Incubator Program Awardees

2013 Awardee: Michael Bulger, PhD

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Dr. Michael Bulger is an Associate Professor of Pediatrics, in the Center for Pediatric Biomedical Research. Dr. Bulger has secondary appointments in the departments of Biochemistry and Biophysics and Wilmot Cancer Center.

Research Interests: Dr. Bulger is interested in the interplay between tissue-specific gene expression and large-scale patterns of chromatin structure, as well as mechanisms by which enhancers and locus control regions (LCRs) mediate gene activation over large genomic distances. He addresses these questions using genes up-regulated or specifically expressed during late erythroid differentiation, including the beta-globin genes, as models

Co-Principal Investigators

James Palis, MD
Professor of Pediatrics (Hematology and Oncology)

Richard Waugh, PhD
Chair of the Department of Biomedical Engineering

Project: Extensively Self-Renewing Erythroblasts as an Ex-Vivo Source of Human Blood

Blood transfusion needs in the U.S., coupled with persistent bottlenecks in donated blood supplies, have created an intense interest in the development of ex vivo methods of producing human red blood cells. The discovery of extensively self-renewing erythroblasts - committed erythroid precursors with unlimited proliferation potential that retain the capacity to differentiate into red blood cells - provides the foundation for a system to artificially generate human blood.

Extensively self-renewing erythoblasts (ESREs) represent committed erythroid precursors that are derived from a narrow window of erythroid ontogeny or from differentiation of embryonic stem cells. Uniquely, however, ESREs possess apparently limitless in vitro proliferation potential while maintaining the ability to produce enucleated red blood cells. As such, they offer the promise of serving as the foundation of a viable system for the ex vivo production of blood. To develop such a system, experiments outlined in this proposal
will serve to (1) derive and optimize conditions for growth of human ESREs, allowing the production of human red blood cells; (2) assemble and test novel bioreactors as a first step toward developing large-scale cultures that would render ex vivo blood production feasible and cost-effective; and (3) utllize ESREs in a high-throughput chemical screen for new chemical therapeutics that could be applied to beta-hemoglobinopathies such as sickle-cell anemia. These approaches will serve as foundational studies to support multiple extramural funding applications aimed at fully developing ESREs as a potential ex vivo source of human red blood cells.

Co-Investigators:

Laura Calvi, MD
Associate Professor of Medicine (Endocrine/ Metabolism)

Alan Smrcka, PhD
Louis C. Lasagna Professorship in Experimental Therapeutics, Professor of Pharmacology and Physiology

 

2012 Awardee: Patricia J. Sime, MD

SimeDr. Sime is Chief of the Division of Pulmonary Diseases and Critical Care in the Department of Medicine. She is also Professor in the Departments of Environmental Medicine, Microbiology & Immunology, and the Cancer Center.

Research Interests: Dr. Sime has a longstanding interest in the mechanisms of pulmonary inflammation and remodeling in diseases such as COPD. She has focused on identifying new therapies for these currently untreatable diseases. Dr. Sime is currently the principal investigator on two NIH grants to study aspects of lung inflammation and fibrosis.

Project: Cigarette smoke, oxidative stress, inflammation and lung injury: Novel therapeutic strategies

Rapid advances are required in the treatment of lung inflammation and remodeling incited by cigarette smoke. Smoking is a major risk factor for all of the leading causes of mortality in the USA including chronic obstructive pulmonary disease (COPD), also called chronic bronchitis and emphysema. Smoking cessation efforts in the US have led to a reduction in the rate of adult smoking from 50% in 1965 to around 20% in 2010, however, there are still 60 million current US smokers and another 50 million ex-smokers at risk for smoking related lung disease. Worldwide, the smoking rate in some countries still exceeds 50%, and it is estimated that COPD will be the 3rd leading cause of death worldwide by 2020. Importantly, while smoking cessation reduces the risk of developing smoking-related diseases, once diagnosed with emphysema, the disease continues to progress even if the patient stops smoking. There are currently no effective treatments that alter the course of the disease or impact mortality. Current therapies such as bronchodilators only provide symptomatic relief. Thus identification of novel inflammatory, oxidative and remodeling targets and development of new therapies are critically needed and are of high impact and significance for human health with significant opportunities for the development of intellectual property.

To address this unmet need, Dr. Sime has assembled a superb team of researchers involved in smoking-related translational lung research with an over arching goal of identifying biomarkers and novel therapies. This multi-departmental team comprises researchers and clinicians from Medicine, Environmental Medicine, Biomedical Genetics, and Public Health Sciences. The central hypothesis is that smoke and other inhalation toxicants incite oxidative and injurious pathways leading to lung inflammation and remodeling (emphysema). Combining 4 synergistic projects, they will identify novel injurious targets including oxidative/carbonyl stress, and test novel therapeutics comprising small molecules and cell based therapies. Few centers anywhere in the world can draw on this spectrum of “team science” spanning basic to translational research.

Co-Investigators:

Dirk Bohmann, PhD
Professor of Biomedical Genetics; Director of the Graduate Program for Genetics, Genomics, and Development; and Director of the Center for Genomics and Systems Biology

Scott McIntosh, PhD
Associate Professor of Public Health Sciences

Richard Phipps, PhD
Professor of Environmental Medicine

Irfan Rahman, PhD
Associate Professor of Environmental Medicine

Tirumalai Rangasamy, PhD
Research Assistant Professor of Pulmonary and Critical Care

Thomas Thatcher, PhD
Research Assistant Professor of Pulmonary and Critical Care

Geoffrey Williams, MD, PhD
Professor in the Departments of Medicine and Psychology

2011 Awardee: Burns Blaxall, PhD

blaxall burnsDr. Blaxall is an Associate Professor of Medicine, within the Aab Cardiovascular Research Institute. He is also Director of the URMC HHMI “Med-Into-Grad” Fellowship program in Cardiovascular Science.

Research interests: The development, progression and regression (treatment) of heart failure, particularly as it relates to beta-adrenergic receptor (beta-AR) signaling.

Project: Novel mixed lineage kinase 3 (MLK3) inhibitors: a single target with therapeutic potential in multiple disease states.

Nearly six million U.S. patients currently suffer from heart failure (HF). This devastating disease has a poor prognosis and effective therapeutic options remain limited. Human immunodeficiency virus 1 (HIV-1) is an equally debilitating disease, and although antiretroviral therapy has transformed HIV-1 infection into a chronic and somewhat manageable disease, HIV-associated neurocognitive disorder (HAND) occurs in more than 50 percent of patients, diminishing quality of life and functionality for daily living.

Although HF and HAND may be viewed as mutually exclusive entities, there are more similarities than previously appreciated. For instance, both diseases are associated with chronic inflammatory and apoptotic states. The awardees have directly implicated the enzyme Mixed Lineage Kinase 3 (MLK3) in inflammatory processes, neuronal apoptosis, and neurodegenerative disease, particularly during HIV infection of the central nervous system. MLKs have also recently been associated with pathologic hypertrophy of isolated cardiac cells. Therefore, inhibiting MLK3 may have therapeutic potential in both HF and HAND.

Drs. Dewhurst and Gelbard have already created a compound that blocks MLK3; it shows great promise in the laboratory. Currently, the entire Rochester team – including Dr. Maggirwar, who will mentor four trainees as part of the grant – is collaborating with Dr. Goodfellow in the ongoing identification and development of a range of MLK3 inhibitor compounds.

The short term goal is to establish the role and therapeutic potential of MLK3 targeting in HF and pathologic intercellular communication. Long term, the project will reveal a new paradigm for pathologic MLK3 and intercellular communication in multiple disease states and will give rise to numerous further interdisciplinary collaborations.

Click here to read more on the proposal and its impact on the University’s future.

Co-Investigators:

Stephen Dewhurst, PhD
Professor and Chair, Microbiology and Immunology

Harris A. Gelbard, MD, PhD
Professor of Neurology and Director of the Center for Neural Development and Disease

Sanjay Maggirwar, PhD
Associate Professor of Microbiology and Immunology

Val Goodfellow, PhD
CEO, Califia Bio, Inc.

 

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