This proposal describes a five-year career development and training plan for Dr. Umesh Sharma under the mentorship of Professor John M. Canty, Jr. Dr. Sharma is currently an Assistant Professor of Medicine at University at Buffalo. His career development plan, that leverages the extensive resources offered by the University and Clinical and Translational Research Center at Buffalo, brings together a strong team of investigators with expertise in small animal physiology, myocardial remodeling, therapeutics and dynamic magnetic resonance imaging. During the period of funding, Dr. Sharma will have a faculty position in the Division of Cardiovascular Medicine at University at Buffalo. His goal is to become a successful and independent investigator studying mechanisms of ischemia-induced myocardial injury and dysfunction, and identify novel therapeutic targets. Receipt of this award will allow Dr. Sharma obtain additional training in small-animal research, comprehensive cardiac tissue and molecular imaging, biostatistics, research design and ethics, and will facilitate his transition to research independence. Dr. Sharma hypothesizes that in presence of ischemic myocardial injury, excess galectin-3 promotes myocardial inflammation and fibrosis. Blocking galectin-3 activity via genetic mutation or therapeutic antagonism inhibits inflammation, reduces fibrosis and preserves cardiac function. Dr. Sharma has a strong research track-record and has obtained excellent preliminary results that show the feasibility of this approach in a murine model of myocardial ischemia. In summary, by bringing together cutting edge technology and a well-rounded team of experts in the setting of excellent research plan and mentorship structure, Dr. Sharma will be able to synergistically merge the fields of advanced imaging, myocardial remodeling and therapeutic targeting using novel liposome-based peptide delivery system. Through this mechanism, Dr. Sharma will obtain support and training to elaborate the skills essential for him to become an independent investigator.

Public Health Relevance

Ischemic myocardial injury leads to progressive loss of cardiac function and development of heart failure. Galectin-3 is a macrophage-derived mediator that can play an important role driving this process, whereas Ac-SDKP has shown anti-galectin-3 effects in vitro. Inhibition of galectin-3 with Ac-SDKP offers new opportunities to prevent and reverse ischemia-induced cardiomyopathies and development of heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL131987-04
Application #
9963046
Study Section
NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
Program Officer
Wang, Wayne C
Project Start
2017-07-15
Project End
2022-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
038633251
City
Amherst
State
NY
Country
United States
Zip Code
14228
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