Incubator Program Awardees

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.

 

 

Co-Investigators:

Dr. Stephen Dewhurst, PhD
Professor and Chair, Microbiology and Immunology

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

Sanjay Maggirwar, PhD
Associate Professor of Microbiology and Immunology

Val Goodfellow, PhD
CEO, Califia Bio, Inc.

Proposal: 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.

 

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.