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.

 

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 kulkarni

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         

courtney jones

Courtney Jones

PhD Candidate, Community & Preventive Medicine

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

Katia 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

Nancy Bennett

Nancy Bennett, MD, MS

Professor, Medicine and Public Health Sciences

Director, Center for Community Health

Associate Vice President, University of Rochester

Comparative Effectiveness of practice-based diabetes prevention programs

The prevention of type 2 diabetes mellitus among all Americans is a critical health challenge, but is particularly pressing among low income and African American populations at higher rates than their white, higher income counterparts. The Diabetes Prevention Program is a proven, cost-effective strategy to prevent pre-diabetics from progressing to diabetes. The Healthy Living Program 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 for the development of an R21 or R01.

John Frelinger

John Frelinger, PhD

Professor, Microbiology and Immunology

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. Local expression of cytokines in the tumor microenvironment by direct injections of cytokines or of viruses encoding cytokines has been remarkably effective at generating immune responses and can result in tumor rejection. However, because cancerous lesions are often numerous and many may not be accessible; translating these advances clinically is difficult. There is a critical need to develop ways in which the cytokine milieu of the tumor microenvironment can be altered using a systemic approach.

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. Our long-range goal is to develop systems that can be tested in preclinical models that can ultimately be translated into patient treatment.

Matthews Jacob

Matthews Jacob, PhD

Assistant Professor, Biomedical Engineering

Member, Computational Biomedical Imaging Group

Improved contrast enhanced cardiac MRI: development and validation

Myocardial first-pass perfusion and late gadolinium enhancement (LGE) schemes are key components of most clinical cardiac MRI exams. The limitations of current MRI schemes often makes it challenging to simultaneously achieve high spatio-temporal resolution, sufficient spatial coverage, and good image quality in first-pass perfusion MRI, resulting in several artifacts. Similarly, the large number of breath-holds and their long duration often makes LGE acquisitions challenging for many patients, resulting in significant motion artifacts and reduced patient throughput.

The main objective of this proposal is to validate our novel regularized reconstruction scheme and pulse sequence to significantly accelerate free-breathing MRI data in a clinical setting. The successful completion of the proposed research will provide quantitative perfusion estimates with a temporal resolution of one heartbeat and spatial resolution of 0.15x0.15x0.8 cc from the entire heart, which is a four-fold improvement over current schemes. Similarly, we expect to considerably improve the patient compliance by relaxing the breath-holding requirement and reducing the scan time in LGE MRI data.

Sherry Spinelli

Sherry Spinelli, PhD

Research Associate Professor, Pathology and Laboratory Medicine

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. Platelets contain abundant amounts of small non-protein coding microRNAs (miRNAs) that have recently been shown to be crucial regulators of cellular function and associated with a wide variety of human diseases, including type-2 diabetes and vascular diseases.

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

Roni Kobrosly

Roni Kobrosly, MPH

PhD Candidate, Public Health Sciences

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

Richard Burac k

Richard Burack, MD, PhD

Director, Hematology Unit, Pathology and Laboratory Medicine

Associate Professor, Pathology and Laboratory Medicine

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.

In summary, while the success of the biorepository is generating proposals which appear competitive for extramural funding, these projects will ultimately compete for a very scarce resource, which may make none practical. 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 Sparks, PhD

Professor, Pathology and Laboratory Medicine

Protein kinase C activation and inhibition of VLDL triglyceride export defines a mechanism for development of non-alcoholic fatty liver disease

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. Recent studies in the Greene laboratory at the Bassett Research Institute have demonstrated that activation of a specific protein kinase C (PKC) isoform is associated with progression of hepatic triglyceride (TG) accumulation (steatosis) to NASH. The Sparks’ laboratory has focused on understanding mechanisms involved in regulated secretion of very low density lipoprotein (VLDL) which is key to hepatic TG export. Preliminary studies indicate that over-expression of atypical PKC in hepatocytes inhibits VLDL TG and apo B secretion while stimulating expression of sterol regulatory element binding protein (SREBP)-1c, a master transcription factor that regulates hepatic lipogenesis. These results suggest the hypothesis that PKC plays a significant role in lipid accumulation by the liver by enhancing lipid synthesis and blocking lipid export via VLDL.

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, Biostatistics and Computational Biology

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 procedure will employ a modified hierarchical clustering method which uses gene differential association as the measure of gene dissimilarity. An algorithm searching for maximal complete subgraph (maximal clique) will also be applied in this procedure.

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, Biostatistics and Computational Biology

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. Since the middle of 1990s, mathematical models described by ordinary differential equations (ODEs) have been widely used for HIV dynamic systems. However, being deterministic, these models have ignored the random disturbances of many biological and environmental factors and the stochastic nature of HIV epidemic process. Stochastic differential equations (SDEs) are natural extensions of the ODEs. The SDE allows us to tease out the stochastic variation of the biological process and random noises, which is useful for clinical and translational longitudinal studies.

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

dani

Danielle de Campo, MS

Student in the Medical Scientist Training Program in Department of Neurobiology and Anatomy

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. This project examines a unique group of immature neurons that may play a vital role in maintaining amygdala structure and optimal function over the lifespan. In collaboration with scientists in Pittsburgh and Oregon, new molecular techniques will be learned to: (1) characterize a population of immature neurons in the amygdala; and (2) understand how these neurons may be altered under conditions of stress. Understanding how these cells are altered by stress will help identify ways to preserve them, possibly averting the negative changes seen in depressions.

Anne Luebke, PhDbennetto

Anne Luebke, PhD

Associate Professor Biomedical Engineering and Neurobiology & Anatomy

Loisa Bennetto, PhD

Associate Professor, Clinical & Social Sciences in Psychology

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.

Krystel Huxlin, PhD

Krystel Huxlin, PhD

Associate Professor, Departments of Ophthalmology, Neurobiology and Anatomy, Center for Visual Science, Brain & Cognitive Science.

Research interests: Adult Visual Plasticity and Physiological Optics

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.

supriya

Supriya Mohile, MD, MS

Assistant Professor, Wilmot Cancer Center.

Research interests: evaluation of health care patterns of care, health outcomes, and quality of life related to treatment for systemic cancer in older 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.

rosero

Spencer Rosero, MD

Associate Professor of Medicine in Division of Cardiology - Cardiac Electrophysiology Laboratory.

Research interests: developing translational device technology such as implantable cell-imbedded biosensors, personalized health monitoring methods for treating patients with heart failure and clinical device-based therapeutics.

URMC is well established in hereditary cardiac ion channelopathies such as Long QT Syndrome associated with sudden cardiac death. The International LQTS registry, based at URMC, is the largest of its kind worldwide with more than 1,000 families, and 25,000 individuals enrolled. The registry provides patient education, and its database includes multi-generation family pedigree data linked to genetic information, clinical phenotype, therapeutic intervention and outcomes data for each individual. The center's clinical research has been directly translated into patient care and played a pivotal role in creating current guidelines for standard of care in the field. We propose to expand our monthly hereditary arrhythmia conference to include other academic centers that are interested in formally contributing to and participating in our conferences.

Anthony Pietropaoli

Anthony Pietropaoli, MD

Associate Professor of Medicine

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.

 

Thomas Thatcher, PhD

Research Assistant Professor, Department of Medicine.

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.

Jennifer Zarcone

Jennifer Zarcone, PhD

Associate Professor, Department of Pediatrics

Research interests: Children with Autism

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 Awardee

Matthew Giannandrea

Matthew Giannandrea, PhD

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. 

2010 UNYTE Awardee

Axel Wismueller

Andrzej Krol

Axel Wismueller, MD, PhD

The Upstate New York Network for Collaborative Biomedical Imaging: Integration of Multimodality, Multispectral and Multidimensional Imaging Data for Breast Cancer Detection, Staging, and Response to Therapy Evaluation.

This project will be conducted in collaboration with Andrzej Krol, PhD, from SUNY Upstate Medical University. The specific aims include: (1) to develop a system for integration, registration, and simultaneous visualization of the above mentioned imaging modalities in breast cancer; and (2) to perform a retrospective quantitative evaluation of the diagnostic benefit that can be achieved by using the integrated image information according to aim 1 in 25 patients with diagnostically challenging breast legions (BI-RADS III-IV).

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2009 Awardees

2009 Faculty Awardees

Susan Fisher

Susan Fisher, PhD

Professor and Department Chair of the Department of Public Health Sciences, and the Director of the Epidemiology doctoral program.

Dr. Fisher's independent research focuses on the investigation of strategies to improve the primary prevention and early detection of cancer in the community. She has directed her efforts toward integrating these epidemiologic and biostatistical concepts into a comprehensive 'evidence-based medicine' approach to medical education. Her pilot project will aim to introduce the concept of a sustainable epidemiologic research partnership to the Rochester community, demonstrate the feasibility of establishing a multi-generational, longitudinal cohort of Rochester residents, and select an appropriate battery of measurement tools and implement a data collection system to support the reliable estimation of health indicators across the life cycle.

Jill Halterman

Jill Halterman, MD, MPH

Associate Professor in the Department of Pediatrics

Dr. Halterman's primary research interests are asthma and Improving quality of care. Her pilot project seeks to improve preventive asthma care for urban adolescents through a feasibility assessment of a new school-based asthma intervention for urban teens. She also aims to evaluate the preliminary effectiveness of that intervention on asthma morbidity, including symptom-free days, adolescent and caregiver quality of life, and urgent care utilizations.

Daniel Mruzek

Daniel Mruzek, PhD

Assistant Professor in Pediatrics

Dr. Mruzek specializes in developmental disabilities with a research interest in Autism Spectrum Disorders. Dr. Mruzek’s project aims to develop a wireless moisture alarm with manualized treatment for daytime urinary continence training of persons with Autism and other disabilities in community and home settings. He also plans to evaluate the treatment effectiveness of this intervention and its corresponding treatment program.

2009 Trainee Awardees

Natalie Cort

Natalie Cort, PhD

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

Dr. Cort aims to conduct a pilot study to examine the feasibility and acceptability of group interpersonal psychotherapy for depressed women with histories of intimate partner violence, and develop treatment guidelines for this population.

Adi Eldar-Lissai

Adi Eldar-Lissai

PhD Candidate in the Health Services Research & Policy program within the department of Public Health Sciences.

Adi plans to study the effect of mass media on geographic variations in cancer treatment outcomes. She will conduct the study through before and after comparisons of exposure to a specific advertisement of a cancer-related drug. She aims to quantify the effect of different levels of community exposure to mass media advertising on changes in treatment patterns, measure the effect of mass media advertising on quality of care, and estimate cost and benefits associated with advertisement of innovative technology.

2009 Clinical Research Center (CRC) Awardee

Elizabeth LeCuyer

Elizabeth LeCuyer, PhD, RN

Assistant Professor in the School of Nursing

Dr. LeCuyer’s project, titled “Diversity in Limit-Setting: African American Mothers with Toddlers,” aims to establish the validity of the Prohibition Coding Scheme (PCS-R), an observational measure assessing maternal limit-setting strategies and links to child self-regulation. Through this pilot project, Dr. LeCuyer hopes to further advance her program of research toward development of interventions for this population.

2009 Trainee Awardee

Ying Xian

Lisa Kakinami

PhD student in the Epidemiology division of the Department of Public Health Sciences

Her research interests include HIV/AIDS, with particular interest in metabolic complications due to HAART and consumer readiness for an HIV vaccine.

Ying Xian

Ying Xian is a physician trained in China and a PhD student in Health Services Research and Policy interested in quality of care and outcomes research in cardiovascular and cerebrovascular disease. He is a recipient of the Predoctoral Fellowship and Young Investigator Seed Grant from the American Heart Association. He was named the AHA Founders Affiliate Bertram Scott Research Fellow for 2008-09.

Their pilot study will compare the energy expenditure between interactive Nintendo Wii Fit games and a moderate intensity aerobic exercise such as walking and running.

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2008 Awardees

2008 Faculty Awardees

jp couderc

Jean-Phillipe Couderc, PhD, MBA

Research Assistant Professor in the Department of Medicine

Dr. Couderc graduated with a MBA from the University of Rochester's Simon School. The title of Dr. Couderc's Pilot project is "A 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. Dr Couderc has dedicated the past ten years to quantitative electrocardiography focusing on the development of novel techniques for the analysis of the ventricular repolarization from the surface ECG in human and in various animal models. Dr. Couderc is the author or co-author of numerous publications in computational science and engineering, numerical analysis, and computer science applied to electrophysiological signals. He is holding a SGE position at the Center for Drug Evaluation and Research for the US Food and Drug Administration. Dr. Couderc is principal investigator and a co-investigator in several federal-funded research grants. He has been invited for lectures at universities, laboratories, and industrial research centers in U.S. and Europe involving consulting experience with industry and national agencies (NIH and EPA).

m jacobs

Matthews Jacob, PhD

Assistant Professor in the Department of Biomedical Engineering and a member of the Computational Biomedical Imaging Group

Dr. Jacob's Pilot project is entitled "Model-based MR Spectroscopic Imaging for Brain Cancer Treatment Planning and Prediction of Recurrence. The Computational Biomedical Imaging Group (CBIG) pursues research on the development of new algorithms for the reconstruction and post-processing of medical and biological images. Dr. Jacob's research interests include image reconstruction, image analysis and quantification in the context of a range of modalities including magnetic resonance imaging, near-infrared spectroscopic imaging and electron microscopy. He obtained his B.Tech in Electronics and Communication Engineering and M.E in signal processing from the National Institute of Technology, Calicut Kerala in 1996 and the Indian Institute of Science, Bangalore in 1999 respectively. He was granted his Ph.D. degree from the Biomedical Imaging Group at the Swiss Federal Institute of Technology in 2003. His PhD dissertation was on parametric shape processing under the guidance of Prof. Michael Unser. He was a Beckman postdoctoral fellow at the University of Illinois at Urbana Champaign between 2003 and 2006.

s karan

Suzanne Karan, MD

Assistant Professor in the Department of Anesthesiology

Dr. Karan's Pilot project is entitled "Physical Therapy for the Airway to Treat Patients with Obstructive Sleep Apnea". Dr. Karan's research interests include Respiratory Physiology, Obstetric Anesthesia, Thoracic Anesthesia, Upper Airway Obstruction, Medical Student Education, and Medical Simulation. She was the recipient of a Research Fellowship Grant from the Foundation of Anesthesiology, Education, and Research (FAER) and was also chosen as a Diplomate by the American Board of Anesthesiology.

Walter ODell

Walter O'Dell, PhD

Assistant Professor in the Departments of Radiation Oncology and Biomedical Engineering

Dr. O'Dell received a Pilot Studies Conference Award for a scientific conference that he is coordinating entitled "Stereotactic Body Radiation Therapy: Innovations and Directions for Clinical Applications". Dr. O'Dell also operates a lab focused on clinical applications of medical imaging in Radiation Oncology that includes novel approaches for screening, treatment and follow-up of cancer patients. Novel 3D tumor detection approaches are being applied for lung, brain and breast screening. Finite element modeling and deformable image registration are being used to quantify the deformation during needle biopsy and radiation damage to healthy tissue surrounding lung tumors. MR DTI is being used in both patient and animal studies to model microscopic tumor spread for treatment planning, with the ultimate hope of minimizing harmful radiation side-effects following high dose radiation treatment.

e porter

Everett Porter, MD

Assistant Professor in the Department of Medicine

Dr. Porter's Pilot project is entitled "CD40 Ligand Mediation of Lung Inflammation and Fibrosis". The project focuses on investigating novel cell to cell interactions responsible for myofibroblast activation, as well as attempting to identify novel biomarkers which can be used to monitor disease progression and response to therapy. Dr. Porter is interested in the clinical management and the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). IPF is an incurable and invariably fatal illness, in which lung fibroblast-to-myofibroblast transformation and the pathologic development of fibroblast foci are believed to play critical roles. Myofibroblasts are believed to be the specialized cells responsible for collagen formation and the fibrotic destruction of alveolar lung units. The presence and numbers of fibroblast foci have been directly correlated with mortality in IPF. He is a previous recipient of a Kirchenstein NRSA grant investigating the role of Heat Shock Protein 70 as an anti-inflammatory agent in preventing myofibroblast activation.

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2007 Awardees

2007 Faculty Awardees

Laura Calvi

Laura Calvi, MD

Assistant Professor of Medicine in the Division of Endocrinology

Dr. Calvi was honored as a Pew Scholar in 2005. Having been raised in Italy through much of High School, Laura attended Union College and then Harvard Medical School, where she took a year out to conduct research. This experience sparked a commitment to research as a career, which extended through training in Internal Medicine and Endocrinology at Massachusetts General Hospital en route to Rochester. In addition to her Pew grant, Dr. Calvi's work has been supported by NIH K08 and K21 awards. Although to date Dr. Calvi's research has mainly used transgenic mouse models, the aim of the pilot is to define changes in the bone and bone marrow in humans that occur as a result of in vivo treatment with parathyroid hormone (PTH). Patients receiving PTH for osteoporosis will undergo prospective bone marrow sampling, with analysis of stem cell and osteoblast compartments. Collaborators include Susan Bukata, MD (Assistant Professor of Orthopaedics) and Jonathan Friedberg, MD Associate Professor of Medicine). The goal is to confirm previous findings in mouse models that PTH exerts a myeloprotective effect. If these mouse findings are found to translate to humans, there would be exciting support for the therapeutic potential of parathyroid hormone (PTH) in a variety of bone and malignant diseases, including bone marrow failure states, and iatrogenic stem cell aplasia due to chemotherapy or radiation.

Charles Duffy

Charles Duffy, MD, PhD

Professor of Neurology

Dr. Duffy received an A.B. in Psychology and Social Relations from Harvard College and went on to the MD-PhD Program at John Hopkins Medical School, earning his PhD in physiology. After an internship at Hopkins in Medicine, he took his Neurology residency at the Massachusetts General Hospital. He was recruited to Rochester as an Assistant Professor in 1993, and rose through the ranks to appointment as Professor in 2003. He is widely recognized for his work on visual-spacial orientation and processing by the brain in normal aging and in Alzheimer's disease. This work is currently supported by two R01 grants, both of which are in years 6-10 of funding. His pilot project, entitled, "VEP's in Aging and Alzheimer's Disease," uses visual evoked potentials (VEPs) to predict a patient's ability to navigate independently based on linked neurophysicological and psychological measures. The information from this pilot and follow-on studies may substantially improve the quality of life for patients who suffer from Alzheimer's disease, which is becoming increasingly important in our aging population.

Becky loy

Rebekah Loy, MPH, PhD

Research Associate Professor of Neurology

Dr. Loy will be spending 3 weeks learning methodology related to epigenetic gene regulation in the laboratory of Dr. Simon D. Spivak at the Wadsworth Research Center. She will then develop techniques that will allow her to test the hypothesis that epigenetic mechanisms may contribute to psychosis and agitation in people with Alzheimer's disease, as well as responsiveness to mood stabilizer therapy.

James McGrath

James McGrath, MD

Associate Professor of Biomedical Engineering

After obtaining his B.S. in mechanical engineering at Arizona State University, Dr. McGrath obtained his PhD in Biological Engineering from the Harvard/MIT program. He was recruited to the Department of Biomedical Engineering in 2001, and became Director of the Graduate Program in Biomedical Engineering in 2004. Dr. McGrath's pilot project, which includes several collaborators [Drs. Jessica Snyder (PhD candidate in Biophysics), Philippe Fauchet (Professor of Electrical Engineering), Alan Friedman (Director of Proteomics Core) and Jeremy Taylor (Nephrology)], will investigate the potential of a novel, silicon-based membrane material (silicon nanomembranes) to provide improvements in hemodialysis that are described as "revolutionary." These membranes are four orders of magnitude thinner (only 15 nm thick) than synthetic and biopolymer membranes currently used in dialysis, which should lead to vastly improved molecular discrimination. This pilot study is the first effort of this group to apply these silicon nanomembranes to solve a specific biomedical problem. It would indeed be a dramatic example of translational science if these ultrathin membranes could be used to improve the lives of patients requiring hemodialysis.

Patricia Sime

Patricia Sime, MD

Associate Professor of Medicine and Environmental Medicine

Born and raised in Scotland, Dr. Sime received her Bachelor's Degree and Medical Degree from the University of Edinburgh and the Royal College of Physicians. She then took her residency training in Medicine in Edinburgh, and a Fellowship in Pulmonary Medicine at McMaster University in Ontario, Canada, where she became interested in adding basic and translational science to her clinical career in pulmonary medicine. She was recruited to Rochester in 1999, received a K08 Award in 2001 and an R01 in 2005 on the molecular mechanisms that explain lung scarring. In this project, Dr. Sime takes advantage of her recent identification of aryl hydrocarbon receptor (AhR) as a previously unrecognized down-regulator of cigarette smoke-mediated inflammatory disease in mice. In the pilot, she and her collaborators (Sanjay Maggirwar, PhD (Assistant Professor of Microbiology & Immunology), Thomas Gasiewicz, PhD (Chair of Environmental Medicine), Michael Larj, MD (Assistant Professor of Medicine), and Richard P. Phipps, PhD (Professor of Environmental Medicine) will attempt to translate their animal model studies to humans by investigating lung tissue, fluid and cells from smokers with and without disease. They will test the hypothesis that activation of AhR dampens human cigarette smoke-induced inflammation. If so, these new studies will identify the AhR as a novel target for future therapy of lung inflammation, and possibly smoking-induced cardiovascular disease.

Xinping Zhang

Xinping Zhang, PhD

Assistant Professor of Orthopaedics

After receiving her M.D. from Shanghai Medical University and her M.S. in Molecular Biology, Dr. Zhang came to Rochester for her PhD training, which she completed in Biochemistry. Dr. Zhang Joined the Dept. of Orthopaedics in 2000 and finished her postdoc training with Dr. Edward Schwarz in 2001. Since then she has been a faculty member in the Dept. of Orthopaedics, Center for Musculoskeletal Research. Her project also has a translational nanotechnology focus, which is one of the innovative science programs emphasized in the URMC Strategic Plan. Specifically, to treat patients with large segmental bone defects, Dr. Zhang proposes a tissue engineering strategy to fabricate a 3D cellular scaffold. Although some work on tissue engineering for the repair of bone defects has been reported, a major limitation has been the lack of a cellular osteoinductive scaffold that could fit around a bone of any size and shape. Dr. Zhang and a multidisciplinary team proposes to use 3D tissue fabrication via electrospinning as a versatile and efficient technique for the fabrication of nanofiber-based scaffolds that match the structural characteristics of extracellular matrix. Included in the team are Dr. Zhang (a bone biologist), Dr. Hong Yang (Associate Professor of Chemical Engineering, an expert in multifunction nanomaterials), Dr. Younan Xia (Professor of Chemistry, U. of Washington, an inventor and pioneer of electrospinning) and Dr. YanFang Ren, (Assistant Professor of Dentistry). Success in these studies on bone tissue engineering would hold much promise for the treatment of bone defects.

2007 Trainee Awardee

anitha krishnan

Anitha Krishnan, MS

PhD candidate in Biomedical Engineering

Anitha has completed her formal coursework. Her efforts are now concentrated on research towards her PhD thesis. Her proposal addresses a critical need for improved treatment of glioblastoma, which currently has a dismal prognosis with current chemotherapy and stereotactic radiotherapy. In particular, radiation treatment is ineffective in protecting against recurrences unless it also treats local spread. However, it lacks the precision required to treat local spread without also ablating a large amount of healthy brain tissue. Anitha seeks to develop and validate predictive models of local cell dispersion using datasets from high resolution in vivo MR diffusion tensor imaging (MR-DTI). It is hoped that such knowledge will lead to prolonged survival of patients with glioblastoma by treating tumor cells that spread out from the primary cancer site, without damaging health tissue.

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