Pilot and Collaborative Studies Awardees

2007 | 2008 | 2009 | 2010 | 20112012 | 2013

2014 Awardees

2014 Faculty Awardees

eliseev

Roman Eliseev, MD

Assistant Professor, Center for Musculoskeletal Research

Improving Mitochondrial Function in Mesenchymal Stem Cells to Accelerate Fracture Repair in Aging

The goal of this project is to test whether improving mitochondrial function in mesenchymal stem cells (MSC) will accelerate fracture healing during aging. In aging, MSC function and osteogenicity are compromised which is suggested to be a reason for delayed fracture healing. Our data and the literature indicate that MSC ability to differentiate into osteogenic lineage depends on their ability to activate mitochondria which are initially inactive in undifferentiated MSCs. Mitochondria in aged MSCs are less active due possibly to the MPT, a non-specific mitochondrial pore regulated by cyclophilin D and frequently observed in aged mitochondria. Thus, inhibition of the MPT is hypothesized to improve MSC mitochondrial function, osteogenicity, and, as a consequence, outcomes of fracture repair in aged mice.

guncial

Elizabaeth Guancial, MD

Assistant Professor of Medicine (Hematology and Oncology)

Chemoprevention of bladder cancer through estrogen receptor modulation

While bladder cancer (BC) has not historically been viewed as a hormone-sensitive cancer, differences in rates of development and prognosis between men and women with BC suggest that estrogens or the estrogen receptor (ER) may be involved in BC carcinogenesis. In vitro studies in BC cell lines demonstrate ER-dependent growth inhibition by antiestrogen agents. Most patients with muscle-invasive BC are unable to receive recommended neoadjuvant or adjuvant chemotherapy due to medical comorbidities and toxicity, despite a high risk of relapse after radical cystectomy alone. Therefore, new treatments are urgently needed to reduce the risk of BC relapse after surgery and for the treatment of advanced BC in patients with other comorbidities. Antiestrogens are commonly used to treat breast cancer and have an acceptable safety profile for most patients. The objective of this project is to investigate the therapeutic role of antiestrogens in the chemoprevention and treatment of BC in order to identify novel therapies that are effective and tolerable and to establish a mechanism of action for these agents through the study of the relative contribution of the two ER subtypes, ERalpha (ERa) and ERbeta (ERb), to BC carcinogenesis in order to identify predictive biomarkers of response to antiestrogens.

looney

R. John Looney. MD

Professor of Medicine (Allergy, Immunology and Rheumatology)

Role of the Gut Microbiome in Preventing Allergic Disease

The epidemic of allergic and autoimmune diseases in developing countries is one of the greatest medical challenges of the 21st century. Although we have greatly improved treatment for many of these diseases, our goal should also be prevention. As discussed above there is considerable data suggesting that the key to this epidemic his how the environment influences immune system development. Finding a population at low risk and comparing immune system development in that population to immune system development in a high risk population is a critical need for this entire area of investigation. The Old Order Mennonite's (OOMs) population of upstate New York provides and an ideal low risk population. The OOMs have a lifestyle incorporating all the various environmental factors that have been associated with a low risk of asthma and allergic diseases including growing up on a farm, having large families, exposure to numerous pets in farm animals, exposure to raw milk, low rate of smoking, and low rate of antibiotic utilization. Our preliminary studies have confirmed at the OOMs did have a markedly lower risk of asthma in the general population in upstate New York. Central Hypothesis – The low rate of atopic disease in children who grow up on farms with numerous siblings is related to accelerated maturation of the immune system due to stimulation of the mucosal immune system early in life by the a diverse microbiome that stimulates innate immune receptors.

messing

Edward Messing, MD

Professor of Urology

Exosomes from bladder cancer patients can serve as biomarkers of disease progression

Bladder cancer is the 5th most commonly diagnosed cancer, the most expensive to treat over the lifetime of the patient, and utilizes the most Medicare dollars. Much of the cost associated with bladder cancer is related to the surgical interventions necessary to diagnose and treat the disease. Moreover, treatment of high-grade bladder cancer is marked with elevated rates of morbidity and mortality (i.e. 36% 5 year survival for pT2 disease). Over the last thirty years there has been very little advancement in chemotherapeutic options for bladder cancer. Identifying markers of tumor progression through less invasive means could expedite treatment, prevent progression, identify novel therapeutic targets and contain cost. Recently an interest in small membrane bound vesicles called exosomes has emerged. Exosomes have been shown to
be important mediators of tumor progression and contain biologically active proteins, messenger (m)RNA, long non coding (lnc)RNA, and micro (mi)RNA. Importantly, exosomes can be readily isolated from blood and urine. We have identified lncRNA and mRNA associated with tumor progression in the exosomes of patients with pT2 bladder cancer suggesting the feasibility of this project.The fundamental goals of this project are to identify stage-specific biomarkers of bladder cancer progression by RNA-sequencing of primary tumors as well as exosomes purified from the urine and blood of patients, and ultimately in downstream experiments identify which of these RNA are important in tumor progression and therefore may serve as targets for anti-sense therapeutics.

morrell

Craig Morrell, DVM, PhD

Associate Professor of Medicine

Novel microRNA Based Therapy to Improve CD4+ T-cell Responses to Vaccination

This project will explore how miR-451 regulates T-cell responses to malaria infection and the use of antagomirs to increase responses to malaria vaccination or infection, representing an important conceptual and therapeutic advancement. These studies will be catalytic in generating new programs and funding for our clinically applicable research. An additional goal of our program is the stimulation of continued crossdisciplinary collaborations between members of the CVRI and Microbiology and Immunology. We will use the combined expertise and knowledge of the Morrell lab, who have extensive experience in animal models of malaria infection), the Lowenstein lab who have published many studies related to miRNA, and the Fowell lab who have great expertise in mechanisms of CD4+ T cell responses.

spinelli

Sherry Spinelli, PhD

Research Associate Professor of Pathology and Laboratory Medicine

The Role of Microparticle-Derived Thy-1 (CD90) in Type 2 Diabetes Mellitus

Thy1 (CD90) is a glycophosphatidylinositol-anchored protein that was discovered decades ago, and recognized simply as a surface marker of unknown function. Recently, our laboratory pioneered studies demonstrating that Thy1 is a key signaling protein that inhibits adipogenesis (fat formation). Thy1 expression down regulates crucial pro-adipogenic factors, such as peroxisome proliferator activated receptor gamma (PPARgamma). While Thy1 was originally identified on the surface of nucleated cells, we have discovered it is present on anucleate platelets and on the platelet progenitor cell, the megakaryocyte. Importantly, Thy1 is also released in platelet microparticles (MPs), thus Thy1 could control adipogenic potential via transcellular regulation in recipient cells. Given the importance of Thy1 in the regulation of adipogenesis and attenuation of proinflammatory adipokines, Thy1 may be an integral player in the pathophysiology of type 2 diabetes mellitus (T2DM), an emerging global epidemic characterized by obesity and a proinflammatory profile. Our group recently detected and measured Thy1 expression in megakaryocytes, platelets and MPs in type 2 diabetics (T2D) versus healthy individuals. Levels of Thy1 were much lower in T2Ds, and importantly, the lack of Thy1 in T2D MPs could be a crucial mediator in upregulating inflammation and adipogenesis in recipient cells.

2014 Trainee Awardees

croasdell

Amanda Croasdell

Medical Student

Specialized proresolving mediators act as novel therapeutics against infection

Nontypeable Haemophilus influenzae (NTHi) is a gram-negative, opportunistic pathogen that commonly causes respiratory diseases, including bronchitis and pneumonia. People with a preexisting inflammatory condition, such as chronic obstructive pulmonary disease (COPD) or an additional infection, are particularly susceptible to NTHi. These infections are increasing in incidence and are often persistent, resulting in bacteria propagating in the airways. Recently, endogenously produced, specialized proresolving lipid mediators (SPMs) were discovered. SPMs play a critical role in the active resolution of inflammation through both anti-inflammatory and pro-resolving actions and are thus strong candidates for use in treating infections. They have been shown to be efficacious in reducing mortality and in decreasing bacteria blood levels through enhanced phagocytosis in mice infected with E. coli. The efficacy of SPMs in promoting resolution of pulmonary infections, however, has not been investigated. My unpublished data shows that SPMs can dampen lung inflammation caused by cigarette smoke or LPS in preclinical mouse models. In human macrophages SPMs increase phagocytosis of bacteria and apoptotic neutrophils.. This research is the first to assess SPMs in pulmonary infections and will provide the groundwork for further investigation and eventual translation of SPMs into a clinical setting.

geba

Daniela Geba

PhD Candidate

Comparative effectiveness of screening methods for type 2 diabetes: a pilot study

The ultimate goal of this project is to compare, in a large-scale randomized clinical trial, the effectiveness of three screening strategies to detect type 2 diabetes: fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and point of care testing (POCT) HbA1c, as they are performed in real clinical settings. Currently, more than one quarter of adult diabetics in the US are undiagnosed and thus at risk of developing diabetes complications by the time of their delayed diagnosis. The panel of approved tests for screening and diagnosis of type 2 diabetes includes only tests performed at central laboratories, such as FPG and HbA1c. Although not approved for this purpose, POCT HbA1c, which is performed at the practice’s site and provides the results within minutes of testing, is used to screen for type 2 diabetes in some clinical settings. Previous studies have focused on the laboratory performance of the screening tests for diabetes, but have not compared their effectiveness when used in real clinical settings.

2014 NBEM Awardees

feng

Changyong Feng

Associate Professor of Biostatistics and Computational Biology

Cure Model in Recurrent Event Data

Although cure model has been studied in traditional survival analysis, for recurrent event data, the case is much more complicated. Unlike the survival data with at most a single event, the observations are censored for study subjects. Some subjects may be cured from the very beginning of the study while some subjects are cured after a few relapses. In this study we will (1) develop a method to test whether the follow-up is long enough to declare some individuals cured; (2) develop nonparametric method to estimate the cure fraction; (3) develop semiparametric method to study the effects of come covariates on the cure probability; and (4) develop a method to make prediction of cure based on some prognostic factors.

hua he

Hua He

Assistant Professor of Biostatistics and Computational Biology

Causal Inference with Zero-inflated Predictors: Alcohol, HIV Risk, and Depression

To make causal inference, we have to compare outcomes between the at- and non-risk groups
separately derived from the theoretical concept of structural zeros. The challenge is that the membership of the two risk groups is unknown for subjects without observed drinking (e.g., 0 in the days of drinking); they may or may not be at-risk, depending on whether they have structural or random zeros. Some recent studies modeled the zero-inflated nature of the count response when they appear as the dependent (or response) variable, but no statistical methodology is available to infer the causal relationships when such variable appears as independent variable. Our goals in this proposal are (1) develop new statistical methods to model the latent membership of the atand non-risk group to enable causal inference of the risk (i.e., an independent variable) on health outcomes; (2) create software for implementing the new statistical methods; (3) test the hypotheses about the role of alcohol on causing (a) depression, and (b) greater frequency of HIV risk behaviors using HANES 2009-2010 data; (4) document the findings as pilot results for our R01 resubmission.

li

Naiji Li

Research Assistant Professor of Biostatistics and Computational Biology

Modeling Human Interactions in Social Networks

The proposed research addresses the lack of methods for modeling and assessing the effect of human interaction on behavioral and health outcomes of socially copnnected individuals. A main premise of this pilot study draws upon recent innovations and methods in the evolving field of data science, a new and burgeoning field that integrates both qualitative and quantative data analytics to draw and capitalize upon Big Data possibilities stemming from mobile and web technologies and social media. We stand on the cusp of a new opportunity due to: improvements in computing, the rapidly growing ubiquity of smart environments, and a resulting duality in contemporary society, that is, the norm of living simultaneously within virtual as well as geophysical proximal interactions and community contexts. Massive amounts of diverse unstructured and structured data about interactions and interventions can now be culled from online sources such as social media, emails, and websites. Mobile devices and online social media such as Smart phones and Twitters generate new potentials over the traditional research paradigm for virtually all disciplines including statistics and its applications to clinical research and practice. Traditional statistical paradigms premised upon individual, within-subject attributes are fundamentally at odds with dependent human interconnections in such data. Well-developed theories of U-statistics and Functional Response Models, along with our experience with leading these theories and applications, positions the proposed proof of concept study to pilot test a new paradigm to model the effect of human interaction on changes of behavioral and health outcomes of socially connected individuals. Further, the software and associated documentation, to be made available via a number of venues including "CTSpedia.org" (a new NIH-funded reference and resource website with a repository of statistical functions to promote multidisciplinary interactions and collaborations), will catalyze the use of such interpersonal, participatory and interactive information from online and mobile sources in disease prevention and health promotion.

2013 Awardees

2013 Faculty Awardees

burack

W. Richard Burack, MD, PhD

Associate Professor, Pathology and Laboratory Medicine

Quantifying Tumor Diversity to predict and target Cancer progression

Biomarkers that predict chemotherapy resistance, relapse and/or transformation risk are critically needed. Because intratumoral genetic diversity is the basis for the evolution of chemotherapy
resistance, relapse, and aggressive transformations of cancers, a metric of genetic diversity has the potential to be a transformative biomarker. Genetic diversity has long been recognized in Follicular lymphoma (FL), a B cell non-Hodgkin Lymphoma that is generally indolent but has a propensity to suddenly transform into a highly malignant form. Follicular B cells normally express an intrinsic genome-damaging enzyme, the APOBEC family member Activation-Induced (Cytidine) Deaminase (AID), an activity required for immunoglobulin diversification. While mutations associated with cancer frequently have the signature sequence of APOBEC/AID targeted loci, data directly implicating AID-induced damage in the generation of intra-tumoral diversification are lacking. Demonstrating this association would suggest a powerful biomarker for risk of progression: greater diversity predicting a greater risk of progression. Making this link requires a quantitative assay that measures AID-dependent intra-tumoral genetic diversity in a high throughput fashion from patients’ specimens, and such an assay has not been reported. Dr. Burack has developed a novel, DNAsequencing based method and analytical approaches to quantify intra-tumoral genetic diversity attributable
to AID.  Dr. Burack’s group will apply this method to typical human tumor specimens to directly test if diversity predicts cancer progression.

calvi

Laura Calvi, MD

Associate Professor, Medicine (Endocrinology)

Osteoblastic Function in Human Leukemia

The mechanisms by which a leukemic clone suppresses normal hematopoiesis are poorly understood, and yet this phenomenon likely contributes to disease progression, disease morbidity and response to therapy. A recent analysis of the bone marrow microenvironment (BME) in a syngeneic mouse model of acute myeloid leukemia demonstrated dramatic osteoblastic defects. Dr. Calvi's laboratory has demonstrated the central role of osteoblastic lineage cells in hematopoietic stem cell (HSC) regulation, these data identify osteoblastic cells as a potential clinical target to stimulate normal HSC recovery in leukemia and decrease BME support of leukemic stem cells (LSCs). Moreover, they discovered leukemic production of the chemokine CCL3, which inhibits osteoblastic function in multiple myeloma. The goal of this pilot project is improving normal hematopoiesis and decreasing microenvironmental support for Leukemic Stem Cells, efficiently, effectively and safely apply pharmacologic tools currently approved for bone anabolic
treatment to leukemia. Data from this project would represent a paradigm shift in the therapy for patients with AML, where targeting of the BME improves our ability to treat the leukemia and more readily restore normal hematopoiesis.

smrcka

Alan Smrcka, PhD

Professor, Pharmacology and Physiology

Inhibition of G protein beta/gamma signaling as a therapeutic approach to treatment of lupus

In complex autoimmune diseases such as Systemic lupus erythematosus (SLE) or rheumatoid arthritis the pathologies are driven in part by alterations of many circulating factors and responsiveness of cells to these factors. Inhibition of a shared signaling mechanism downstream from these receptors, that operates both in the adaptive and innate immune system, will likely result in higher efficacy than specific pathway or factor targeting. One such pathway is the G protein beta/gamma subunit signaling pathway downstream of the chemokines receptors that control the migration activation and survival of all types of immune cells. Dr. Smrcka has identified a compound that inhibits G protein beta/gamma subunit-dependent signaling in isolated human neutrophils, inhibits neutrophil migration in vitro, and inhibits acute inflammation in mice by preventing neutrophil migration and activation at sites of inflammation. Dr. Smrcka plans to test the viability of Gbeta/gamma inhibition as a treatment paradigm for lupus and to test anovel hypothesis that Gbeta/gamma inhibition ameliorates disease by acting at both the innate and adaptive immune system. Dr. Smrcka will collaborate with Jennifer Anolik, MD, PhD, Associate Professor of Medicine (Allergy/Immunology and Rheumatology) on this project.

2013 Trainee Awardees

Hsimin Hsiao

Hsi-min (Jim) Hsiao, BS, MS

Pathology and Laboratory Medicine

Novel pro-resolving lipid mediators reduce cigarette smoke-induced emphysema

Chronic obstructive pulmonary disease (COPD, emphysema and chronic bronchitis) is the fourth leading cause of death in the United States. Importantly, the disease continues to worsen even after smoking cessation. Current therapies for COPD attempt to relieve the symptoms but do not alter the course of the disease; therefore, new therapies for COPD are desperately needed. This study will provide critical pre-clinical data needed to prepare for human clinical trials of resolvins in lung disease. A multidisciplinary collaboration has also been established to analyze the effects of resolvins on lung function, inflammatory response, cell death and signaling cascades, including clinically relevant measures such as pulmonary function testing, to increase the translational potential.

Jonathan Stone

Jonathan Stone, BA, MD

Neurosurgery

Intraparenchymal Stent for Obstructive Hydrocephalus (IPSOH): a Novel Technology

Hydrocephalus is a common debilitating neurologic disease affecting a significant portion of the pediatric and adult population. The current surgical treatment options are frought with complications and excessive costs heralding the need for new technology. Futhermore, the pathophysiological effects of hydrocephalus and fluid shunting on brain interstial fluid are unknown and need further investigation to improve patient care. This project will not only test the efficacy of this new shunt system in an animal model, but will also evaluate the movement of interstial fluid in hydrocephlaus and after both interventions.

2013 UNYTE Awardees

bernstein

Steven Bernstein, MD

Professor of Medicine (Hematology and Oncology)

Lymphoma and its microenvironment; a novel in vivo model to study its interplay

Follicular lymphoma is an incurable disease with conventional therapy and thus new approaches for treatment are needed. As the lymphoma cells require signals from the other non-malignant cells in the tumor (the tumor microenvironment) to survive, targeting such interactions represents a novel approach for treatment. Recent data shows that the FL immune microenvironment, particularly the distinct T-cell populations infiltrating the tumor, play a critical role in modulating the biology and clinical behavior of this disease; however an understanding of how these populations modulate FL B-cell growth, viability and sensitivity to immune-chemotherapy (IC) is lacking. The investigators are now poised for the first time to test the central hypothesis that the interplay of FL Tregs and Tfh either directly or indirectly modulate FL B-cell growth, viability and sensitivity to IC in vivo.

Ankur Chandra

Ankur Chandra, MD

Assistant Professor of Surgery (Vascular Surgery)

Regional Ultrasound Wall Strain Measurements to Predict Risk of AAA Rupture

Two-hundred thousand new Abdominal Aortic Aneurysm (AAA) cases are diagnosed each year in the United States; fifteen thousand people die from AAA rupture each year, making it the 13th leading cause of death in this country and affecting 1 in 250 individuals over 50 years of age. The exact cause of AAA formation is still unknown, although many theories base their pathogenesis as a multifactorial cause. Creating a “strain fingerprint” to determine the probability of a rupture is a viable new option that could significantly decrease AAA deaths.The project goal is to develop a novel application of existing ultrasound strain algorithms as a transcutaneous imaging modality to predict the risk of AAA rupture, regardless of size.

2013 NBEM Awardees

Anthony Almudevar

Anthony Almudevar, Bsc, Msc, PhD

Associate Professor of Biostatistics and Computational Biology

Predictive Models for Longitudinal Technological Home Monitoring Data

The aim of this proposal is to develop preliminary data and a proof-of-concept demonstration to leverage future research. The CB assessment application is particularly suitable for a number of reasons. The number of alternative assessment tools is limited to self-reporting, psychometric testing, or direct interview. We note also the availability of processed data from two parallel monitoring systems for caregiver/patient dyads, which is a highly specialized and uncommon scenario.

Changrong Feng

Changyong Feng, PhD

Associate Professor of Biostatistics and Computational Biology

Allowance for center effects in the analysis of randomized clinical trial with time-to-event outcomes

Many randomized clinical trials (RCT) have time-to-event outcomes. The log-rank test is widely used to analyze such event-time data as it is the most efficient nonparametric test under the hypothesis of proportional hazards. However the log-rank test assumes that individuals in the same treatment group are all homogeneous. Heterogeneity among individuals in a randomized study does not invalidate the log-rank tests, but it may make it less efficient. It is common to control heterogeneity using a stratified log-rank test (SLRT). It is known that if there is substantial heterogeneity among centers, the SLRT will be more sensitive to treatment differences than the unstratified test (here denoted ULRT). On the other hand, unnecessary stratification can lead to a loss of efficiency. However the trade-off between these two situations is still not well understood. In some practical situations the ULRT appears to be more sensitive than the SLRT even when there is quite substantial heterogeneity between Centers. In this proposal we will compare the relative efficiency of SLRT and ULRT under two different scenarios and obtain an optimal linear combination of these test statistics which maximize the power.

Xing Qiu

Xing Qiu, PhD

Assistant Professor of Biostatistics and Computational Biology

A Unified Method for Differential Expression and Differential Association Analyses

Thousands of basic research projects use the microarray technology, yet very few of them have been successfully translated into clinical applications. This proposal responds to this challenge by integrating normalization, DE analysis, and DA analysis, in such a way that not only the computational cost is reduced, but also the false positives/negatives are reduced by using one MTP for both analyses simultaneously.

2012 Awardees

2012 Faculty Awardees

neil blumberg

Neil Blumberg, MD

Professor, Pathology and Laboratory Medicine

Improving Platelet Storage and Transfusion Outcomes with PPARγ Ligands

Platelet transfusion is the most commonly used therapy for patients with trauma, hematologic diseases or cancer who are experiencing bleeding and low platelet counts. Our proposed investigations are vitally important, since in the USA alone, almost two million platelet transfusions are given each year. Poorly understood mechanisms that occur during platelet storage, termed the “platelet storage lesion”, reduce platelet transfusion efficacy and safety. Consequently, patients are transfused not only with partially or abnormally activated platelets that reduce transfusion efficacy, but also with storage supernatants containing many potentially harmful bioactive mediators that can elicit adverse responses to transfusion. For example, platelet transfusion can cause alloimmunization, fever, rigors, and allergic reactions. A critical barrier to the prevention of adverse post-platelet transfusion events is the absence of approaches to modify storage conditions that ameliorate the platelet storage lesion. Hence, there is an urgent need to investigate new targets to attenuate platelet activation mechanisms, thus improving the efficacy and safety of platelet storage.

Our objective is to focus on novel aspects of platelet biology to better understand the mechanisms that drive unwanted platelet activation during storage, leading to the development of new technologies of platelet storage that will maintain normal platelet quality and function.

lisa delouise

Lisa DeLouise, PhD, MPD

Associate Professor, Dermatology

High throughput sorting of rare cells from blood using Microbubble Arrays

Development of monoclonal antibodies (mAbs) for therapeutic use is a rapidly growing $50 billion/year market. Hybridoma technology is a time tested technique used to generate antibodies; but it is costly to screen all clones generated and therefore quality antibodies

maybe missed. Non-animal techniques that can identify and characterize ASC in peripheral human blood that exhibit high binding specificity and affinity are in high demand. Microbubbles are novel compartments formed in an optically clear elastomeric material. MBs exhibit unique properties for cell culture which are leveraged in this screening application that provides many advantages over existing techniques.

Our project seeks to advance development of a new high throughput cell screening technology based on microbubble (MB) arrays. Based on preliminary studies we will investigate the development of MB arrays to to enrich, identify, characterize, and recover rare antigen specific antibody secreting (ASC) from peripheral blood. This project will investigate the limits of this assay and to automate the data acquisition and analysis.

ajit

Ajit Kulkarni, PhD

Research Assistant Professor, Medicine (Pulmonary/Critical Care Division)

Characterization of antifibrotic effects of CDDO, a small electrophilic compound

Pulmonary Fibrosis compromises normal lung function and structure due to scarring of lung tissues. Scarring is caused by proliferation of fibroblasts and myofibroblasts, and excess deposition of extracellular matrix proteins in fibrotic foci. There is an urgent unmet need to develop new therapies for pulmonary fibrosis since effective treatments are often lacking.

We have reported that a small electrophilic compound, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) inhibited the transforming growth factor (TGF)-β induced differentiation of human lung fibroblasts to myofibroblasts (scar forming cells) in vitro. We hypothesize that by inhibiting myofibroblast differentiation and proliferation, and by inhibiting expression of pro-fibrotic genes by fibroblasts and myofibroblasts, we will be able to slow or arrest the progress of the disease in patients with lung fibrosis. Here, we will investigate the efficacy of CDDO in vivo using models of pulmonary fibrosis. We hope these studies will rapidly lead to a new therapy for patients with suffer from pulmonary fibrosis.

Yang Liu

Yang Liu, BM, PhD

Research Assistant Professor, Neurosurgery

Therapeutic targeting of CXCR7 in malignant glioma by small molecule antagonist

Malignant gliomas represent a uniformly fatal form of cancer. Despite advances in neurosurgical techniques, chemotherapeutic regimens and radiotherapy protocols, little improvement has been made in the 5-year relative survival rates of brain tumor patients during the past several decades. Glioblastomas, the most common and highest grade of malignant glioma, are highly vascular, highlighting a potential therapeutic target. Chemokines and their receptors play critical roles in many physiological and pathological processes, including brain cancer. Chemokine receptor 7 (CXCR7) was recently identified as second receptor for stromal cell derived factor 1 (SDF1) and exerts an important role in tumor growth and vascularization.

Previously, we found that CXCR7 mRNA was expressed at levels 9 times higher in brain tumors than normal brain samples and was localized to vascular regions within glioma samples. We also found that inhibition of CXCR7 expression by targeted siRNA significantly impeded glioma cell proliferation and motility in vitro and limited intracranial xenograft growth and improved mouse survival, validating CXCR7 as a potential therapeutic target for glioma. Furthermore, recent studies have shown that SDF1 can recruit bone marrow derived endothelial progenitor cells to tumor neovessels and attract haematopoietic progenitor cells to intracerebral glioma. Therefore, we propose that SDF1/CXCR7 play an important role in brain tumor growth and maintenance of the vascular niche between brain tumor stem cells and the neurovasculature.

2012 Trainee Awardee         

c jones

Courtney Jones

PhD Candidate (Epidemiology), Public Health Sciences

Developing an age-specific decision scheme for prehospital triage of injured older adult

Injury is among the leading causes of death and disability for older adults. Treatment at advanced care hospitals specializing in injury, also known as trauma centers, has been shown to significantly improve patient outcomes. However, the selection of a receiving hospital is dependent upon emergency medical services (EMS) providers making appropriate clinical judgments in the prehospital setting – a process referred to as trauma triage. It is known that older adults are less likely to receive trauma center care than younger adults, but reasons for this age-based disparity are not well understood. Evidence suggests two mechanisms are involved: 1) EMS providers' decision-making process differs for older adults compared to younger adults; and 2) the current guidelines to aid EMS providers in their trauma triage decisions are inadequate to identify older adults who require trauma center care. This proposal aims to assess both of these potential reasons by using a combination of analytic methods. As the number of older adults in the US is projected to increase dramatically in future years, injury will continue to be a major burden on the public's health. Identifying and addressing reasons for the age-based disparity in trauma center care is vital to improving patient outcomes for this population.

2012 UNYTE Awardee

noyes

Katia Noyes, PhD, MPH

Professor, Public Health Sciences

Validity of Self-Reported Data for Studying Cognitive Problems and Depression

MS is the most common neurologic disease affecting young adults, striking nearly 500,000 people in the US. MS-related symptoms include physical disability, fatigue, cognitive impairment, and affective disorders. MS is different from most of other chronic conditions: its financial impact associated with person's productivity, social functioning, and employment is nearly as significant as the economic burden of medical treatment. The prevalence of major depression in patients with MS (16%) is over twice that among chronically ill population without MS (9%), and nearly four times higher than in general population (4%). Hence, it is critical that the research community takes concrete steps toward resolving the uncertainty surrounding the optimal treatment of individuals suffering from MS, particularly those with affective and cognitive dysfunction.

The main goal of this study is to assess validity of self-reported information about cognitive and mental health status in patients with multiple sclerosis (MS) and to understand feasibility of using these data for quality of care assessment and program evaluation. This study aims to stimulate and enhance our cross-disciplinary collaboration between the Departments of Public Health Sciences and Neurology, University of Rochester and Baird MS Center in Buffalo, NY. The study will involve two sites (University of Rochester and University of Buffalo/Jacobs Neurologic Institute in Buffalo, NY) of the New York State Multiple Sclerosis Consortium, one of the largest databases of MS patients.

2012 Novel Biostatistical Epidemiological Methods (NBEM) Awardees     

hua he

Hua He, PhD

Assistant Professor, Biostatistics and Computational Biology

Novel models for analyzing drinking outcomes: A pilot study comparing competing approaches

The COMBINE Study was conducted from 2001 to 2004, with 1,383 individuals of alcohol dependence assigned to one of nine pharmacological and/or psychosocial treatment conditions. The only other alcohol treatment study in the U.S. on this scale was Project MATCH, conducted in the early 1990’s. COMBINE compared two promising pharmacological treatments for alcoholism, naltrexone and acamprosate, alone and in combination with an combined behavioral intervention (CBI). Although the primary outcome papers of COMBINE have been published, researchers are at an early stage in exploiting the potential of this dataset to address questions beyond a comparison of its treatment conditions.

This application addresses an important statistical issue in alcohol research: the analysis of a bounded count response with structural zeros and overdispersion within a longitudinal data setting. This issue is highly relevant to the analysis of treatment effectiveness of drinking interventions for various risk populations. We will develop a new approach for such zero-inflated binomial-based (ZIB) count response for cross-sectional and longitudinal studies, and use it as a benchmark to evaluate the performance of the approaches that either have been used for analyzing such count responses in the alcohol research literature or existing alternatives in the statistical literature, such as zero-inflated Poisson (ZIP) model, general regression model for transformed count response and Hall & Zhang's marginal models for ZIB, by conducting intensive simulation studies and applying them to drinking outcomes in COMBINE.

Rui Hu

Rui Hu, PhD

Research Assistant Professor, Biostatistics and Computational Biology

Detecting Intergene Association Changes in Microarray Data

Microarray technology has become a routine gene expression analysis tool in recent years. Biomedical researchers rely on this technology to identify potentially “interesting” genes. Typically, individual genes are tested for their differential expressions between phenotypes by the two-sample Student’s t-test or its nonparametric counterpart. The resulting p-values are adjusted by a chosen multiple testing procedure (MTP) in order to control certain group-wise Type I errors.

We plan to develop a novel gene selection procedure based on intergene association structure changes across different phenotypes. Gene differential association analysis which was explored in our preliminary study utilized the gene association vector in the gene selection, which provided quite conservative testing power. In this study, we will focus on gene pairs and search for most powerful statistical tests to detect differential associated genes.

yinglin xia

Yinglin Xia, PhD, MS

Research Assistant Professor, Biostatistics and Computational Biology

Integrative Analysis of Pathways to SA and PPD in High Risk Families

This proposal is to develop a new class of statistical models to facilitate integrative analysis of multi-faceted data and to illustrate the new methodology by applying it to examine pathways to suicide attempts (SA) in high risk families using the GenRED database. The feature-rich GenRED database provides a rare and unique opportunity to explore the types of risk factors and what roles they play in the pathways to SA. Significant advances have been made over the past few decades in the theory and applications as well as software development for fitting structural equation models (SEM). However, our recent work shows that there are several limitations in existing methods.

Our goals in this proposal are to (1) test hypotheses of SA using existing standard SEM, (2) develop a class of distribution-free SEM, (3) test hypotheses using the new methods. Specifically, we will create a dataset using GenRED to examine the following set of hypotheses concerning pathways to SA using existing SEM.

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2011 Awardees

2011 Faculty Awardees

bennett

Nancy Bennett, MD, MS

Director of the Center for Community Health

Co-Investigators: Jennifer Carroll, MD, MPH, Linda Clark, MD, MS, Michael Nazar, MD, and James Sutton, PA.

Project: Comparative Effectiveness of practice-based diabetes prevention programs

The Healthy Living Program, a community-developed program, adapted from the evidence-based Stanford program, and conducted in community settings has been ongoing in the Rochester community since 2001 and has had over 1,700 participants in both the original program targeting African Americans and the revised program, Vida en Salud, for the Latino community. We propose to compare the effectiveness and costs of the two programs through a randomized trial conducted at primary care practices. In addition, we will study the feasibility of collecting data regarding the behavioral/motivational mechanisms through which these programs are successful. This pilot will enable the team to design the optimal study, refine endpoints and measurement instruments, explore the feasibility of randomization in a community health center clinical setting, and collect pilot data to determine effect sizes.

frelinger

John Frelinger, PhD

Professor of Microbiology and Immunology

Co-Investigator: Mark Sullivan, PhD

Project: Protease activated cytokines: a novel methodology for the delivery and activation of cytokines

Cytokines play critical roles in cellular immune responses. The immunotherapy of cancers with cytokines has had some dramatic clinical successes, but side effects limit their use when delivered systemically. We are developing a novel approach that employs a fusion protein (FP) in which a cytokine is joined to its specific binding moiety; an antibody fragment (scFv) identified using phage display, separated by a protease site. The strategy is that before cleavage, the cytokine is largely inactive, but that after cleavage by a protease expressed at the tumor site, the cytokine can become available to interact with high affinity receptors on immune cells.

Sherry Spinelli

Sherry Spinelli, PhD

Research Associate Professor of Pathology and Laboratory Medicine

Co-Investigators: Richard Phipps, PhD, Charles Francis, MD, and Stephen Hammes, MD, PhD

Project: Microparticle miRNAs as transcellular messengers in diabetes and vascular disease

Microparticles (MPs) are submicron-sized membrane vesicles that are released into the blood by platelets and vascular cells. MPs contain cellular information in the form of bioactive proteins, lipids and molecules that influence cells, not only in the region of their release, but are carried in the circulation to elicit broad-reaching transcellular effects. A major knowledge gap is in understanding the mechanisms that govern MP transcellular communication. This research plan will investigate MPs derived from healthy and type-2 diabetic individuals. The hypothesis is that altered packaging of miRNAs in platelet MPs is a key element in vascular cell communication that may promote inflammation. We predict that differences in miRNA levels and types could serve as biomarkers of disease progression and lead to therapeutic strategies to modulate cellular dysregulation.

2011 Trainee Awardee

kobrosly

Roni Kobrosly, MPH

PhD Candidate in the Department of Public Health Sciences (Epidemiology)

Co-Investigators: Edwin van Wijngaarden, PhD, (primary mentor), Jan Moynihan, PhD, Deborah Cory-Slechta, PhD, Christopher Seplaki, PhD

Project: Examining the link between allostatic load and depressive symptoms among the elderly

Allostatic load is a developing epidemiologic concept that has been used to quantify the physiologic costs of cumulative life stress, whether psychological or physical. Although various forms of life stress have been linked with late-life depressive symptoms, the association between allostatic load and depressive symptoms has never been assessed. This proposal entails a cross-sectional study of approximately 200 community dwelling older adults examining the complex relationship of life stress, allostatic load, and psychosocial factors with the severity of late-life depressive symptoms. One specific aim and one exploratory aim are detailed: (1) to examine the relationship between allostatic load and the severity of depressive symptoms, and, as an exploratory aim, (2) to conduct a path analysis to examine the complex causal web of biological, psychological, and social factors underlying late-life depressive symptoms.

2011 UNYTE Awardees

burack

Richard Burack, MD, PhD

Associate Professor of Pathology and Laboratory Medicine

Co-Investigator: Robert Hutchison, MD (SUNY Upstate Medical University)

Project: Regional stat tumor procurement to support studies of lymphoma

A major barrier to studying cancer and its treatment is the limited availability of human tumors. To address this problem, the NCI funds biorepositories such as the lymphoma-specific biorepository at URMC, a component of the NCI-funded SPORE in lymphoma at URMC. While tumor “banks” are common, the focus of the URMC biorepository on viable specimens is perhaps unique in the country, and has been critical to obtaining NCI-funding for projects at URMC. The availability of this resource has spurred interest in studying lymphoma, all with important technologies and/or hypotheses that could be reasonably tested given sufficient materials. However, current NCI-funded programs are using essentially all the specimens obtained at Strong Memorial Hospital/URMC. Demonstrating a regional lymphoma biorepository focused on stat distribution of living lymphomas to researchers will be critical to several proposals under development for submission to the NCI and NIH.

Janet Sparks

Janet Dehoff-Sparks, PhD

Professor of Pathology and Laboratory Medicine

Co-Investigator: Michael Greene, PhD (Bassett Research Institute)

Project: Protein kinase C (PKC) activation and inhibition of VLDL triglyceride (TG) export

Obesity is associated with non-alcoholic fatty liver disease (NAFLD) which can progress to the more serious condition of non-alcoholic steatohepatitis (NASH), a known precursor to cirrhosis and hepatocellular carcinoma in humans. In this proposal we examine the extent to which specific hepatic PKC isoforms regulate hepatic TG balance. Results will provide evidence to support a pharmacologic approach to reduce hepatic steatosis by blocking PKC signaling specifically in the liver thereby reducing lipogenesis and enhancing VLDL TG export.

2011 Novel Biostatistical Epidemiological Methods (NBEM) Awardees

Rui Hu

Rui Hu, PhD

Research Assistant Professor of Biostatistics and Computational Biology

Co-Investgators: Sandhya Dwarkadas, PhD, Galina Glazko, PhD, Xing Qiu, PhD

Project: Clustering Differentially Associated Genes

We plan to develop a novel gene clustering procedure based on gene differential association analysis which was explored in our preliminary study. By applying this procedure to microarray gene expression data, we can search for differentially associated gene groups such that genes belonging to the same group do not change their association structure across different phenotypes while the association structure of genes from different groups are differentiated across phenotypes. This novel procedure has the ability to uncover biologically meaningful gene groups which contain differentially associated genes. Consequently, it can complement and enhance the existing clustering algorithms based on differentially expressed genes. It will also help us understand how the phenotypic differences of gene dependence structure can be used to cluster genes into biologically meaningful units.

Honqi Xue

Hongqi Xue, PhD

Research Assistant Professor of Biostatistics and Computational Biology

Project: Parameter estimation for nonlinear stochastic differential equation models from noisy longitudinal data in HIV dynamic research

In AIDS research, one major area is to model the interaction between HIV virus and the immune cellular responses. It is very useful for understanding the pathogenesis of HIV infection and assessing the potency of antiviral therapies. The investigator is focusing on the following four aims: (1) To develop multidimensional nonlinear SDE models for modeling the interaction between HIV virus and the CD4+ T cells for HIV-infected patients under treatment; (2) To develop parameter identifiability methods for such models with noisy longitudinal data; (3) To develop novel parameter estimation methods with sound theoretical justifications and computational efficiency for such models; and 4) To develop novel model selection methods between SDE models and ODE models.

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2010 Awardees

2010 Faculty Awardees

luebke

Anne Luebke, PhD

Associate Professor of Neurobiology & Anatomy

Loisa Bennetto, PhD

Associate Professor of Clinical & Social Sciences in Psychology

Project: Efferent Feedback and Hearing-in-Noise Perception in Autism and Typical Development

Our overall hypothesis is that physiological-based biomarkers of cochlear efferent strength will be impaired in the autism spectrum disorder (ASD) population. The specific aim of the project is to determine efferent feedback strength in children and adolescents with ASD when compared with typical controls (age, gender, and IQ matched). We will build on existing measures of MOC strength using two different otoacoustic emission-based tests with short and sustained binaural broadband suppression to obtain maximal efferent feedback strength in both ears of all participants.

bennetto
Krystel Huxlin, PhD

Krystel Huxlin, PhD

Associate Professor of Ophthalmology

Co-Investigators: Richard Phipps, PhD, Steven Feldon, MD, MBA, and Holly Hindman, MD.

Project: A Novel Anti-Ocular Scarring Molecule

Scarring in the cornea is mediated by specialized fibroblasts called keratocytes. When these cells get stimulated as a result of injury, infection, dry eye, corneal transplantation, LASIK, etc., they change into a cell called a myofibroblast. The myofibroblast produces excess collagen and alpha smooth muscle actin. The cells and their matrix now become light reflective. This feature causes corneal haze, decreasing vision quality. We have discovered that a small molecule called ITE known to bind to a transcription factor called the aryl hydrocarbon receptor, interferes with the ability of eye fibroblasts to develop into scar-forming myofibroblasts. We have two objectives. Assess the ability of ITE to inhibit different aspects of TGF-induced myofibroblast differentiation from primary human corneal fibroblasts in culture. The second objective is to assess the ability of ITE to prevent corneal scarring in vivo using a novel preclinical mouse model.

mohile

Supriya Gupta Mohile, MD, MS

Assistant Professor of Medicine (Hematology and Oncology)

Co-Investigators: Karen Mustian, PhD, MPH; Pascal Jean-Pierre, PhD; Gary Morrow, PhD; William Hall, MD.

Project: Novel Physical Activity Interventions for Older Prostate Cancer Patients

Prostate cancer is an age-associated disease, with a median age of diagnosis of 79 years. The use of androgen deprivation therapy (ADT), the mainstay of treatment for systemic prostate cancer, is rising in older men. ADT, by depleting testosterone, leads to significant side effects such as muscle wasting, increased fatigue, and reduced physical stamina. Our primary objective is to compare the effects of two innovative, tailored, multi-component exercise intervention strategies, developed collaboratively by our cross-disciplinary research group, on the physical performance of prostate cancer patients aged 70 or over receiving ADT.

pietropaoli

Anthony Pietropaoli, MD, MPH

Associate Professor of Medicine (Pulmonary and Critical Care)

Co-Investigators: Paul Brookes, PhD and Alan Friedman, PhD

Project: Effect of Inflammatory and Oxidative Stress on Erythrocyte Nitric Oxide Metabolism

Exciting new evidence indicates that the vasodilator nitric oxide (NO) can be stored, transported, and delivered in the circulation, effectively matching blood flow to metabolic need. Current theories propose that plasma nitrite is converted to NO in resistance arterioles by the catalytic activity of partially deoxygenated erythrocytes (RBCs).The circulatory consumption of nitrite results in a measurable arteriovenous (AV) nitrite concentration difference. Hypothesis: Erythrocytes exposed in vitro to oxidative or inflammatory stress develop RBC membrane protein modifications that impair RBC nitrite and NO metabolism. We plan to conduct in vitro experiments measuring the effects of oxidative stress and inflammatory stimuli, known mediators of sepsis pathophysiology, on RBC nitrite and NO metabolism and RBC membrane proteins.

sime

Patricia J. Sime, MD, FRCP

Associate Professor of Medicine (Pulmonary and Critical Care)

Co-Investigators: Ramil Sapinoro PhD, Richard P. Phipps PhD, Charles Serhan PhD

Project: Anti-inflammatory and Pro-resolving Lipid Mediators: Their role in regulating lung inflammation

Chronic inflammation is central to the development of numerous human diseases including pulmonary diseases such as COPD, asthma, pulmonary fibrosis, ARDS, and following certain infections. It was previously thought that resolution was a passive process, but recent emerging research has identified that resolution is an active process and that dual acting lipid mediators called resolvins have both anti-inflammatory and pro-resolving actions. The hypothesis to be tested in this application is that metabolites (resolvins) promote the resolution of neutrophilic lung inflammation incited by cigarette smoke and other lung injuries and toxicants.

thatcher

Thomas Thatcher, PhD

Research Assistant Professor of Medicine (Pulmonary and Critical Care)

Co-Investigators: Patricia Sime, MD, Thomas Gasiewicz, PhD, and Alexandra Livingstone, PhD

Project: The Aryl Hydrocarbon Receptor as a Novel Regulator of Allergic Lung Inflammation

Asthma is a chronic disease affecting nearly 30 million Americans, including 10 million children. Although major strides have been made in understanding and controlling this disease, it is sill associated with significant personal and financial costs to society. Understanding the mechanisms that lead to allergy and asthma is crucial to the development of new therapies. We hope to determine the mechanism by which AhR deficient DCs promote a Th2 bias and increased allergic airway inflammation and determine the effects of different AhR ligands on T cell programming by DCs both in vivo and in vitro.

wellington

Melanie Wellington, MD, PhD

Assistant Professor of Pediatrics (Infectious Disease)

Co-Investigator: Damian Krysan, MD, PhD

Project: Tamoxifen as an adjunctive agent in antifungal therapy

Preliminary data indicate that the direct antifungal activity of tamoxifen is not quite sufficient to warrant its use as a single agent but its disease and immunomodulatory properties in combination with its intrinsic activity offer a potentially useful role as an adjuvant to other therapies. The most direct route to translate these findings into clinical use is to demonstrate that a combination of tamoxifen and a standard antifungal agent is more efficacious than the standard agent alone in an animal model of systemic candidiasis. In combination, the killing activity of the standard agent would be augmented by the disease- and immuno-modulatory properties of tamoxifen. If combination therapy proves efficacious, the fact that the human pharmacology of tamoxifen is well studied and it is already approved for human use means that combination therapy could be rapidly moved to human clinical trials. Therefore, we propose to test the efficacy of tamoxifen in combination with three standard antifungal drugs currently in clinical practice (fluconazole, caspofungin, and amphotericin B) using a mouse model of systemic candidiasis already in use in our laboratory. Specifically, we will treat infected mice with placebo, each agent singly, and combinations

Jennifer Zarcone

Jennifer Zarcone, PhD

Associate Professor of Pediatrics

Co-Investigators: Elizabeth McAnarney, MD, and Madalina Tivarus, PhD

Project: Evaluating set shifting in adolescents with restrictive anorexia nervosa (RAN) using fMRI: A cross-disciplinary, collaborative study

The long-term goal of this research is to develop a clinical intervention research program for anorexia and other eating disorders in adolescents. The short-term goal is to develop a neurobehavioral model of set shifting and subsequently use this model to develop a targeted intervention program. The specific aims are: (1) to establish a cross-disciplinary, collaborative relationship between the Department of Brain and Cognitive Sciences, the Rochester Brain Imaging Center, and the Department of Pediatrics in the study of the neurobehavioral etiology of set shifting in females with RAN; (2) to define the neurobehavioral origins of set-shifting deficits by conducting set-shifting tasks during fMRI on female adolescents who have RAN and compare their findings to those of age- and IQ-matched controls; and (3) to use the data from this study and from other cross-disciplinary collaborations in the development of an NIH proposal for an intervention program for adolescents with RAN.

2010 Trainee Awardees

Matthew Giannandrea

Matthew Giannandrea, PhD

Post-doctoral Fellow in the Department of Microbiology and Immunology

Mentor: B. Paige Lawrence, PhD

Co-Invesigators: Michael O'Reilly, PhD and Steve Georas, PhD

Project: Consequences of Neonatal Oxygen Supplementation to Long-Term Respiratory Health

Respiratory illnesses consistently represent one of the top ten causes of death in the United States each year. Certain populations are at an increased risk due to underlying conditions that affect their susceptibility to infection or their response to airborne allergens.  Specifically, premature newborns, which required supplemental oxygen after birth are more frequently hospitalized due to respiratory viral infections and have increased incidence of asthma symptoms compared to infants born at term.  These infants are often diagnosed with bronchopulmonary dysplasia (BPD); a chronic lung disease broadly associated with impaired lung development that leads to poor lung function as children and into adulthood. While the survival rate of premature babies diagnosed with BPD continues to increase, health care spending is also likely to rise due to their increased risk of hospitalization.  The long-term goal of this project is to understand how oxygen supplementation during the neonatal period results in susceptibility to respiratory viral infection and asthma.  In particular, by understanding the changes occurring within the immune system we will be better able to devise appropriate treatments to improve the respiratory health of individuals with BPD. 

selzler

Katherine Selzler

PhD Candidate in the Department of Neurobiology and Anatomy

Mentor: Mark Mapstone

Project: Understanding Mechanisms of Deep Brain Stimulation on Prefrontal Cortex in Parkinson's Disease

The goal of this project is to understand how the basal ganglia modulate frontal cortical function and resultant behavior in humans. We will study the neurophysiological and behavioral effects of subthalamic nucleus (STN) stimulation on prefrontal cortex in Parkinson's disease (PO) patients treated with bilateral STN deep brain stimulation (OBS). We hypothesize that STN stimulation for PO related motor disability also affects cognitive functions supported by frontal cortical regions. The findings from this study will be directly used to guide electrode placement and stimulation parameters in the application of OBS as an effective therapy for PO motor disability while minimizing cognitive side effects for future patients.

2010 Travel Awardee

dani

Danielle deCampo, MS

MD/PhD Candidate (Neuroscience Graduate Program) in the Department of Neurobiology and Anatomy)

Mentor: Julie Fudge, MD

Project: Genetic expression profile of immature neurons in the primate amygdala: Substrate for plastic change

The amygdala is a brain region that exhibits abnormal structure and function in mood an anxiety disorders. Stress, a frequent precipitant of these disorders may directly shape amygdala structure and function by altering how neurons grow and communicate. Our research plan has a twofold purpose: 1) generate new information about amygdalar immature neurons that would otherwise be too costly and timeconsuming to be feasible, and 2) establish techniques to examine the expression profile of immature cells under conditions of chronic stress (nonhuman primates) and mood disorders (human post-mortem).

 

2010 UNYTE Awardee

wismueller

 

Axel Wismueller, MD, PhD

Associate Professor of Imaging Sciences

Co-Investigators: Andrzej Krol, PhD (SUNY Upstate Medical University), Markus B. Huber, PhD (UR), Wei Lee, PhD (SUNY Upstate Medical University), Avice O’Connell, MD (UR), Jennifer Barna, MD (SUNY Upstate Medical University)

Project: The Upstate New York Network for Collaborative Biomedical Imaging

Accurate and complete integration of all available complementary information from multiple imaging sources is an extremely demanding and time-consuming task that often exceeds the capabilities of the human visual and cognitive system, as well as conventional resources available to radiologists. To accomplish this aim, coherent integration, registration, and simultaneous visualization of multidimensional image data is necessary: It is the crucial obstacle that has to be overcome to make such information accessible to clinicians, prevent repeated imaging procedures, and improve clinical outcomes. To address this urgent need, the newly formed Upstate New York Network for Collaborative Biomedical Imaging (UNY-NCBI) proposes a scientific project on the accurate and efficient integration and simultaneous visualization of multimodality, multispectral and multidimensional image data for the diagnosis of cancer.

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2009 Awardees

2009 Faculty Awardees

fisher

Susan Fisher, PhD

Professor of Public Health Sciences

Co-Investigators: Edwin van Wijngaarden, PhD, and Nancy Bennett, MD, MPH

Project: Development of a Sustainable Community Cohort for Translational Research

The specific goals of this pilot project are: 1.) to introduce the concept of a sustainable research partnership to the Rochester community; 2.) to demonstrate the feasibility of establishing a multi-generational, longitudinal cohort of household residents in the Rochester area; 3.) to establish operational systems for the reliable estimation of health indicators across the life cycle. The long term goals of this research initiative are two-fold: to examine the role of obesity as a ubiquitous inflammatory risk factor for cancer, and to provide a future research laboratory for translational investigators across the University and the region.

halterman

Jill Halterman, MD, MPH

Associate Professor of Pediatrics

Co-Investigators: Belinda Borrelli, PhD, and Kristin Riekert, PhD

Project: A Pilot Study to Improve Preventive Asthma Care for Urban Adolescents

In collaboration with the school district and school nursing program, we propose to pilot an innovative school-based asthma program to enhance the delivery of preventive health care for 12-15 year old children with significant asthma. This program is based on our prior work and our ties to the school district, and includes two key components. First, a partnership with the school nurse will be established to assure that the teen receives appropriate daily preventive asthma medications. The teen will visit the nurse daily at school to receive directly observed delivery of preventive medications for the first 6-8 weeks of the program. During this time, the second component will begin. This component consists of a nurse-led guided self management program to help the teen transition to independence with preventive medication use. A trained nurse clinician will conduct three counseling sessions with the teen, using principles of motivational interviewing, that are designed to enhance the teen’s motivation to change health behaviors, with a focus on adherence to evidencebased preventive care guidelines (e.g.; preventive medications). Motivational interviewing is particularly appropriate for teens, because it is a patient-centered counseling technique designed to enhance motivation based on the teen’s individual needs and developmental level. When the teen is ready to fully implement their self-management plan, they will transition to independent use of daily preventive medications.

mruzek

Daniel Mruzek, PhD

Assistant Professor of Pediatrics

Co-Investigator: Stephen McAleavey, PhD

Project:Development of a Wireless Moisture Alarm for Daytime Urinary Continence Training of Persons with Autism and Other Disabilities in Community Settings

It is hypothesized that use of the wireless treatment alarm and corresponding manualized treatment program for toilet training persons with developmental disabilities for whom traditional toilet training strategies have proven ineffective will result in effective toilet training with a high degree of consumer satisfaction. The specific aims of this study are as follows:
a. Develop a wireless moisture alarm (WMA) for use in behaviorally-based urinary continence training of persons with autism and other developmental disabilities in community based settings
b. Develop a manualized treatment progmm for toilet training persons with autism and other developmental disabilities
c. Evaluate the treatment effectiveness of the WMA and corresponding treatment program in urinary continence training in persons with autism and other developmental disabilities in community settings.

2009 Trainee Awardees

cort

Natalie Cort, PhD

Post-Doctoral Fellow (Clinical Psychology) in the Department of Psychiatry

Co-Investigators: Nancy L. Talbot, PhD., Ellen L. Poleshuck, Ph.D., Catherine Mazzotta, L.C.S.W

Project: Group Interpersonal Psychotherapy for Psychologically Distressed Women with Histories of Intimate Partner Violence (IPV-IPV): A Pilot Study

IPT, which explores the interpersonal context in which depression occurs, has demonstrated effectiveness in multiple clinical trials and is beneficial in group and individual treatment of posttraumatic stress disorder (PTSD). However, IPT has not been tested with depressed and traumatized women with IPV histories. IPT-IPV will add IPV-specific elements, such as education about the effects of IPV, to IPT in a manner entirely consistent with the manualized treatment. This pilot study is the first step leading to a NIMH National Research Service Award for Individual Postdoctoral Fellow (F32) application to investigate the effectiveness of IPT-IPV. My long-term aim is to improve public health through the development of community-based interventions for abused women that are tailored to address the mental health attitudes and treatment needs of African American women .

Adi Eldar-Lissai

Adi Eldar-Lissai

PhD Candidate (Health Services Research & Policy) in the Department of Public Health Sciences

Co-Investigators: Charles E. Phelps, PhD, Katia Noyes, PhD, MPH, Gary H. Lyman, MD, MPH, Peter J. Neumann, ScD

Project: The Effect of Mass Media on Geographic Variations in Cancer Treatment Outcomes

Through the application of suitable statistical and econometric methodologies, this study will be the first to empirically measure the effect on health outcomes associated with mass media communication. The detailed measures of changes in various health outcomes are expected to create new knowledge and provide significant indications for policy makers, examining whether more balanced mechanisms to increase patients’ understanding and involvement in their medical decisions are needed. Conducting this study will allow the trainee (Adi Eldar-Lissai) to obtain and improve new skills such as developing statistical models to measure health outcomes derived from complex administrative datasets.

Ying Xian

Lisa Kakinami

PhD Candidate (Epidemiology) in the Department of Public Health Sciences

Ying Xian

PhD Candidate (Epidemiology) in the Department of Public Health Sciences

Co-Investigators: Karen M. Mustian, PhD, MS, Diana Fernandez, MD, MPH, PhD

Project: Is the Wii Fit Good Enough? A Comparison of the Energy Expenditure from Interactive Physical Activity

This study will provide preliminary data tor {iilure external grant applications comparing the EE of 4 different PA conditions employing cutting-edge interactive P A promoting technology among adults. Specific Aim: To provide preliminary data comparing the EE of 30 minutes of treadmill walking/running, 30 minutes of Wii Fit Free Running and 3 bouts of Wii Fit Advanced Step, Super Hula Hoop, and Rhythm Boxing each lasting 10 minutes

2009 Clinical Research Center Awardee

Elizabeth LeCuyer

Elizabeth LeCuyer, PhD, RN

Assistant Professor in the School of Nursing

Project: Diversity in Limit-Setting: African American Mothers with Toddlers

The findings of this pilot would accordingly provide essential data for further study targeting intervention development. If ethnic differences are found, the data would provide evidence for a longitudinal study similar to the investigator's prior work, but with AfricanAmerican dyads, linking early limit-setting behaviors to children's social competence, self-concept, delay of gratification, and also problem behavior. If ethnic differences are not found, the findings would provide evidence for a proposal testing an intervention assisting mothers to facilitate their children's development of self-regulation through optimal limit-setting. Ethnically diverse data is thus crucial for this program of research.

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2008 Awardees

2008 Faculty Awardees

jp couderc

Jean-Philippe Couderc, PhD, MBA

Research Assistant Professor of Medicine (Cardiology)

Co-Investigators: Arthur Moss, MD, David Bushinsky, MD, Hongwei Zhao, ScD, Daniel Gray, MD, PhD, Wojciech Zareba, MD, PhD

Project: Proof-of-concept Study for Assessing the Interest of Novel ECG technologies in the Risk Stratification of Patients with End Stage Renal Disease: Using the Hemodialysis Session as an Arrhythmic Challenge.

In this proposal, we designed a proof-of-concept study to enable a cross-disciplinary research program between the Cardiology, the Nephrology and the Biostatistics Departments at University of Rochester (UofR). The objective is to develop ECG technologies for the prediction of sudden cardiac death in end-stage renal disease (ERSD) patients. Over the past 2 years, our laboratory has developed ECG tools to help pharmaceutical companies in the assessment of drug cardiotoxicity linked to ion-kinetic dysfunctions. We believe that a novel set of ECG technologies may be developed specifically for the risk stratification of ESRD patients in whom large changes in electrolytes concentrations and fluid shifts occur during dialysis. Today, the cardiac monitoring following dialysis is not used because of the lack of meaningful ECG markers.

m jacob

Mathews Jacob, PhD

Assistant Professor of Biomedical Engineering

Co-Investigators: Tianliang Gu, PhD, Sven Ekholm, Walter O'Dell, PhD, Jianhui Zhong, PhD, Giovanni Schiffito, MD, Delphine Davis, PhD

Project: Model-based MR spectroscopic imaging for brain cancer treatment planning and prediction of recurrence

The main objective of this project is to develop a robust, high-resolution MRSI scheme that can provide whole brain coverage in a reasonable scan time. Such an MRSI scheme will revolutionize the treatment of brain cancer, thus significantly improving the survival rates. To achieve this goal, we propose to merge our novel model-based reconstruction algorithm with our echo-planar spectroscopic imaging (EPSI) sequence and the eight-channel head coil. The reconstruction algorithm alone provides a significant reduction in artifacts and signal losses, while reducing the scan time by five fold. At the same time, the new EPSI sequence yields a factor of four increase in the spatial resolution. In addition, the use of the eight-channel coil on the 3T scanner provides up-to a factor of four gain in sensitivity. Our central hypothesis is that the combination of our reconstruction algorithm with the new EPSI sequence and the eight-channel head coil will provide an MRSI scheme that will significantly improve spatial resolution, sensitivity, scan time, and reproducibility.

s karan

Suzanne Karan, MD

Assistant Professor of Anesthesiology

Project: Physical Therapy for the Airway

Physiologically, the respiratory response to negative airway application differs between wakefulness and sleep as a result of the cortical drive to maintain upper airway patency. The upper airway negative pressure that naturally generates during sleep causes insufficient tonic and phasic drive to the muscles (hence the airway collapse) in OSAS patients.  When CPAP therapy is prescribed, there is no tone in the muscles.  Thus, both in treated and untreated OSAS, there is no conditioning of the upper airway muscles during sleep.  The key to our proposed therapy is the use of NAP when awake so that the increased reflex phasic drive to the muscles will result in muscle conditioning.  Interestingly, other studies have indicated that upper airway muscle training may be useful in treating OSAS, but these studies used techniques that were not scientifically designed or used a technique (electrical stimulation) that was not well tolerated.

 

e porter

Everett Porter, MD

Assistant Professor of Medicine (Pulmonary and Critical Care)

Co-Investigators: Patricia Sime, MD and Richard Phipps, PhD

Project: CD40 Ligand Mediation of Lung Inflammation and Fibrosis

This pilot proposal will generate novel evidence for CD40 Ligand (CD40L, formally known as CD154) as an important mediator in the pathogenesis of lung fibrosis. This proposal has a translational focus, and includes both clinical and basic science research aims. It will be directed by a complementary team comprising a physician (Everett Porter, interstitial lung disease), a physician-scientist (Patricia Sime, lung fibrosis and fibroblast biology), and a basic researcher (Richard Phipps, immunology, fibroblast biology and CD40-CD40L interactions). Dr. Phipps has published numerous papers on CD40 and CD40 interactions in immune and structural cells, and his laboratory has significant expertise in this area. Patients will be recruited from a newly created Interstitial Lung Disease Clinic (Patricia Sime, MD, Director).

2008 Conference Awardee

walter odell

Walter O'Dell, PhD

Assistant Professor in the Departments of Radiation Oncology and Biomedical Engineering

Co-Investigators: Michael C. Schell, PhD and Paul Okunieff, MD

Project: Scientific Conference in Stereotactic Body Radiation Therapy: Innovations and Directions for Clinical Application

Our aim is to organize and run a small 50-80 person scientific conference on SBRT , comprised of the current world leaders in SBRT related research and clinical application. This 2-day conference will bring together experts in the field to share ideas, present innovative research and clinical findings, and work towards furthering collaborations between researchers, clinicians and industry. Specific topics will include: 1) radiation delivery (IMRT, beam filtering, dose fractionization schemes); 2) real-time lesion tracking and position verification; 3) tissue heterogeneity correction; 4) specific applications to lung, liver, and spine; 5) tissue response and radioprotection. An ancillary aim of this conference is to solidify our department’s image as leader in the field of extracranial radiotherapy and as a hub for communication and collaboration for SBRT related research and clinical implementation.

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2007 Awardees

2007 Faculty Awardees

Laura Calvi

Laura Calvi, MD

Assistant Professor of Medicine (Endocrinology)

Co-Investigators: Susan V. Bukata MD, Dr. Jonathan W. Friedberg MD

Project: In vivo effects of PTH on osteoblasts and hematopoietic stem cells

The specific aim of this pilot study is to define changes in the bone and bone marrow that occur as a result of in vivo treatment with parathyroid hormone. This represents an evolving collaboration, directly translating Dr. Calvi’s basic stem cell research to potential clinical applications in both the Musculoskeletal Center (Dr. Bukata), and the Cancer Center (Dr. Friedberg). We expect that results will generate hypotheses, and clinical trials to evaluate the therapeutic potential of PTH in a variety of bone and malignant diseases including bone marrow failure states, and iatrogenic stem cell aplasia secondary to chemotherapy or radiation. In this regard, pilot funding for this proposal has the ability to be catalytic in terms of generating a new research program and direction for the collaborators, and has significant potential to lead to funding for clinically applied research in the near future.

duffy

Charles Duffy, MD, PhD

Professor of Neurology

Co-Investigators: Voyko Kavcic, PhD, Laura Cushman, PhD

Project: VMEPs in Aging and Alzheimer's Disease

We have developed a new approach to assessing cortical involvement in the functional impairments of Alzheimer’s disease (AD). Using visual evoked potentials (VEPs) we have elicited robust cortical responses by presenting the radial patterns of visual motion that simulate observer self-movement, optic flow. Our preliminary work revealed a remarkable relationship between scalp-recorded responses evoked by optic flow and navigational capacity, allowing us to predict a patient’s ability to navigate independently based on linked neurophysiological and psychophysical measures. This new technology has tremendous potential applications to: 1) the detection of AD deficits in pre-symptomatic older adults, 2) the therapeutic monitoring of established and investigational interventions, 3) and the assessment of fitness for driving and independent living. This project will also enhance the value of the US patent granted to UofR (per C. J. Duffy) on this technology.

james mcgrath

James McGrath, MD

Associate Professor of Biomedical Engineering

Co-Investigators: Alan Friedman PhD, Jeremy Taylor MD, Philippe Fauchet , PhD

Project: Ultrathin silicon membranes for revolutionary improvements in hemodialysis

This project will investigate the potential of a novel, silicon-based, membrane material (silicon nanomembranes or SN membranes) to provide revolutionary improvements in hemodialysis. Improved transport efficiency is expected because SN membranes are four orders of magnitude thinner (only 15 nm thick) than synthetic and biopolymer membranes currently used in dialysis. Improved molecular discrimination is expected because SN membranes have sharp cut-offs in the size range of key blood proteins, whereas commercial membranes have poorly defined cut-offs. Our published and unpublished experiments support the predicted benefits of SN membranes for molecular separations. This key design objective remains unmet by existing hemodialysis membranes. A successful pilot project will imply that SN membranes can be used for more effective, faster, and smaller (portable) dialysis systems.

sime

Patricia Sime, MD

Associate Professor of Medicine and Environmental Medicine

Co-Investigators: Sanjay Maggirwar, PhD, Thomas Gasiewicz, PhD, Michael Larj, MD, Richard Phipps, PhD

Project: Novel mechanisms and therapeutic targets in human cigarette-smoke induced inflammation

We propose to translate our animal model studies to humans by investigating lung tissue, bronchoalveolar lavage fluid, and primary human structural cells (fibroblasts and epithelial cells) from smokers with and without lung disease. We will test for expression of AhR and we will examine the hypothesis that activation of the AhR dampens human cigarette smoke-induced inflammation (as well as inflammation mediated by certain other respiratory toxicants). These new studies will identify the AhR as a novel target for future therapy of lung inflammation induced by cigarette smoke, as well as other inflammatory stimuli. We predict these new findings will also be relevant to patients with smoking-induced cardiovascular disease/atherosclerosis, as well as those with smoking-related cancers.

xinping zhang

Xinping Zhang, PhD

Assistant Professor of Orthopaedics

Co-Investigators: Hong Yang, PhD, Younan Xia, PhD, Yanfang Ren,PhD, MD, DDS, MPH

Project: Electrospun Fibers of Instructive Nanocomposites for Stem Cell Based Bone Tissue Engineering

Here we propose a multidisciplinary team among a bone biologist (XZ), an expert in multifunctional nanomaterials (HY), and a well-known inventor and pioneer of electrospinning (YX), to establish the suitability of electrospinning and fabrication the 3D cellular scaffold as a matrix for bone tissue engineering. It should be noted that the development of this platform technology for tissue engineering and the utilization of our mouse model with highly innovative outcome measures will have broad applicability to many CTSI investigators in other fields of research. Furthermore, it will have great ramifications for a wide range of clinical and basic translational studies involving biomimetics, stem cell and tissue engineering.

2007 Travel Awardee

Becky loy

Rebekah Loy, MPH, PhD

Research Associate Professor of Neurology

Project: Gene Promoter Methylation in Alzheimer’s Disease

Our overall goal is to determine if behaviorally-relevant changes in expression of selected molecular targets are regulated by epigenetic pathways, and if chromatin modification can be a strategic therapeutic target for psychosis and mood disorders. My overall aim in bringing this novel methodology to the University of Rochester will be to help develop collaborative studies for non-invasive risk profiling, therapy monitoring and preventive and early disease detection strategies.

 

2007 Trainee Awardee

anitha krishnan

Anitha Priya Krishnan, MS

PhD candidate in Biomedical Engineering

Mentor: Walter G. O'Dell, PhD

Project: Modeling Brain Cancer Dispersion for SRT using MR Diffusion Weighted Imaging

This study is the first cross-disciplinary collaboration between the four contributing departments and represents a novel application of MR imaging to the clinically troubling concern of treatment of aggressive brain cancer. Ms. Krishnan will be expected to become engrossed in all aspects of this project, from implementing DTI post-processing software; assisting with the animal engraftment and imaging; developing and testing the computational migration model; and, with Through this unique collaborative team Ms. Krishnan will be exposed to biological laboratory techniques, state-of-the art MR imaging, numerical computation, and the clinical cancer care environment.

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NIH Funding Acknowledgement ** Important ** All publications resulting from the utilization of CTSI resources are required to credit the CTSI grant by including the NIH FUNDING ACKNOWLEDGEMENT and must comply with the NIH Public Access Policy.