Ruhul Abid, MD

Assistant Professor of Surgery (Cardiothoracic Surgery)
Rhode Island Hospital
Alpert Medical School at Brown University
CORO WEST 5th Floor, Room 5.231
Providence RI 02903
ph: 401.863.1000
ph 2: 401.444.6527

ruhul_abid@brown.edu


Ruhul Abid, MD

Bio

Ruhul Abid, MD, PhD is the Principal Investigator of the Project #3 (Improvement of Coronary Vascular Function by Endothelium-targeted Increase in Reactive Oxygen Species) of the CardioPulmonary Vascular Biology COBRE (PI: Rounds). He is also a Principal Investigator at the Cardiovascular Research Center (CVRC) at Rhode Island Hospital and Assistant Professor at the Alpert Medical School of Brown University.

Dr. Abid received his MD from Dhaka Medical College with special training on hypertension and related diseases. He also served as the Project Leader of a PHC (Global Health) project with special emphasis on communicable and non-communicable diseases including cardiovascular and maternal health care in Bangladesh. Dr. Abid received his PhD in Molecular Biology and Biochemistry from the Graduate School of Science, Nagoya University, Japan, and did his postdoctoral training in breast cancer at the LSU Medical Center, LA, USA. He then joined Harvard Medical School and completed a Fellowship in Vascular Medicine at Beth Israel Deaconess Medical Center. He began his career at Harvard Medical School as an Instructor in Medicine in 2002, rising to the rank of Assistant Professor in 2006. He joined Brown Medical School as Assistant Professor in 2011 and has established his vascular biology lab at the CVRC of Rhode Island Hospital. He has been serving on the Medical Faculty Executive Council of Alpert Medical School since 2012.

Dr. Abid has combined careers in research on vascular biology, cardiovascular diseases, and teaching of graduate students. Basic science research interests include mechanisms of coronary circulation in health and disease (e.g. myocardial ischemia), signal transduction in vascular endothelial cell, and effects of reactive oxygen species on vascular/endothelial function and angiogenesis. He has published original research articles in many peer-reviewed journals. He has been continuously supported by research grants from the American Heart Association and NIH since 2004. In recognition of his research achievements, Dr. Abid was honored by the American Heart Association with the prestigious Werner Risau New Investigator Award in Vascular Biology in 2011. Dr. Abid is also the recipient of the 6th annual Young Investigator Award in Thrombosis from the ATVB, American Heart Association in 2005. He has served as a member of the study sections for the American Heart Association, Association for International Cancer Research (AICR), and NIH (adhoc- VCMB). He has been serving as a full member of the Lipids, Thrombosis, and Vascular Wall Biology-Clinical (LTVWB-Clinical) Study Section since 2008. Dr. Abid has mentored many residents, postdoctoral fellows, medical and undergraduate students during his tenure at HMS and Brown Alpert Medical School.

Ruhul Abid will utilize his extensive experience in both research and training to fulfill the goals of the CardioPulmonary COBRE to enhance cardiovascular research in the State of Rhode Island.

COBRE Abstract

Ischemic heart disease (IHD) or myocardial ischemia is a disease characterized by tissue hypoxia due to reduced blood supply to the heart muscle, usually caused by coronary artery disease. IHD is the leading cause of death and morbidity in the USA. Increase in coronary vessel diameter by vasodilatation (acute response), and increase in vessel density (delayed response) are two major defenses of myocardium from ischemic insults. While coronary vasodilatation is primarily dependent on endothelium-generated nitric oxide (NO), the increase in capillary density initially requires proliferation and migration of vascular endothelial cells (ECs). Increased levels of reactive oxygen species (ROS) are often observed in many cardiovascular diseases, including IHD, giving rise to the notion that ROS cause endothelial dysfunction. However, recent major interventional clinical trials using antioxidants (e.g. HOPE, ATBC), have largely produced negative results in reducing primary endpoints of cardiovascular death and morbidity. Reports from our lab demonstrated that reduced ROS levels inhibited signal transduction events that are essential for NO generation in the vascular endothelium and for coronary vasodilatation. Preliminary Results also showed that c-Src responds to changes in endothelial redox levels and promotes downstream PI3K-Akt signaling, which in turn activates eNOS and inhibits the growth inhibitory transcription factor, FOXO1, in coronary vascular ECs. This application will test a novel HYPOTHESIS that conditional increase in endothelium-specific-ROS will activate c-Src-PI3K-Akt-eNOS pathway and inhibit FOXO1, and thus, will result in coronary vasodilatation and increased vessel density in a myocardial ischemia model in vivo. Utilizing a newly developed binary transgenic mice that can induce conditional expression of Nox2 and 2-fold increase in ROS in vascular endothelium, we will determine whether EC-ROS activate c-Src-PI3K-Akt signaling, proliferation and migration of mouse heart ECs in vitro (Aim 1); whether EC-ROS induce PI3K-Akt-eNOS activation, NO synthesis and coronary vasodilatation (Aim 2); and whether EC-ROS increase vessel density in ischemic myocardium in an LAD ligation model in vivo (Aim 3).

Public Health Relevance:
The main objective of this proposal is to examine whether condtional increase (1.8±0.42-fold for 2 weeks) in EC-ROS improves coronary vascular tone and/or collateral vessel formation in the ischemic myocardium. The long-term goal is to develop redox-based novel therapeutic modalities that will ‘pre-condition’ coronary endothelium to improve coronary circulation in myocardial ischemia/infarction. Using novel binary transgenic mice (Tet-Nox2/VE-Cad-tTA) that, upon withdrawal of tetracycline, can induce 1.8±0.42-fold increase in EC-specific ROS in vivo, we propose the following Specific Aims:

Publications

Links to the papers published:

  1. Feng J, Damrauer SM, Lee M, Sellke FW, Ferran CJ, Abid MR*. Endothelium-dependent Coronary Vasodilatation Requires NADPH Oxidase-derived ROS. 2010. Arterioscler Thromb Vasc Biol. 2010 Sep; 30(9):1703-10. (*Corresponding Author) PMCID: 20702812
    PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/20702812
  2. Lee, M, Choy WC, Abid MR. Direct Sensing of Endothelial Oxidants by VEGFR-2 and c-Src. PLoS ONE. 2011;6(12):e28454. PMCID: 3228784
    PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/22145046
  3. Sun Z, Li X, Massena S, Kutschera S, Padhan N, Gualandi L, Sundvold-Gjerstad V, Gustafsson K, Choy WW, Zang G, Quach M, Jansson L, Phillipson M, Abid MR, Spurkland A, Claesson-Welsh L. VEGFR2 induces c-Src Signaling and Vascular Permeability in vivo via adaptor TSAd. J Exp Med. 2012 Jul 2;209(7):1363-77. PMID: 22689825
    PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/22689825
  4. Shafique E, Choy WC, Feng J, Lyra A, Clements R, Bianchi C, Benjamin LE, Sellke FW, Abid MR. Oxidative Stress Improves Coronary Endothelial Function through Activation of the Pro-survival kinase AMPK. Aging. 2013 Jul; 5(7):515-30. PMID: 24018842
    PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed/24018842
  5. Dharaneeswaran H, Abid MR, Yuan L, Dupuis D, Beeler D, Spokes KC, Janes L, Sciuto T, Kang PM, Jaminet SC, Dvorak A, Grant MA, Regan ER, Aird WC. FOXO1-mediated activation of Akt plays a critical role in vascular homeostasis. Circ Res. 2014 Jul 7; 115(2):238-51. doi: 10.1161/CIRCRESAHA.115.303227.
  6. Abid MR, Sellke FW. Antioxidant Therapy: Is it your Gateway to Improved Cardiovascular Health? Pharm Anal Acta. 2015 Jan;6(1). pii: 323. PMID: 26005589
  7. Potz BA, Sellke FW, Abid MR. Endothelial ROS and Impaired Myocardial Oxygen Consumption in Sepsis-induced Cardiac Dysfunction. J Intensive Crit Care. 2016;2(1). pii: 20. PMID: 27135058
  8. Sabe AA, Potz BA, Elmadhun NY, Liu Y, Feng J, Abid MR, Abbott JD, Senger DR, Sellke FW. Calpain inhibition improves collateral-dependent perfusion in a hypercholesterolemic swine model of chronic myocardial ischemia. J Thorac Cardiovasc Surg. 2016 Jan;151(1):245-52. doi: 10.1016/j.jtcvs.2015.08.101. PMID:26478238
  9. Potz BA, Sabe AA, Abid MR, Sellke FW. Calpains and Coronary Vascular Disease. Circ. J. 2016: 80(1):4-10. doi: 10.1253/circj.CJ-15-0997. PMID: 26489456
  10. Potz BA, Sabe AA, Abid MR, Sellke FW. Calpains and Coronary Vascular Disease. Circ J. 2016;80(1):4-10. doi: 10.1253/circj.CJ-15-0997. PMID: 26489456
  11. Abid MR. A Conceptual Guide to the Measurement of Different Reactive and Nitrogen Species in Cardiovascular Tissue. Available in: American Heart Association Learning Library. https://professional.heart.org/professional/ScienceNews/UCM_486803_A-Conceptual-Guide-to-the-Measurement-of-Different-Reactive-Oxygen-and-Reactive.jsp . Posted July 16, 2016.
  12. Reichert, K, Colantuono B, McCormack I, Rodrigues F, Abid MR. Murine Left Anterior Descending Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction. JoVE, 2016, JoVE55353R1 (in-press).
  13. Abid MR, Sellke FW. Subcellular ROS Signaling in Cardiovascular Disease. Free Radicals and Diseases. Ed. Rizvan Ahmad. Croatia, European Union: InTech Open Science, 2016; in press. ISBN: 978-953-51-2746-8
Project Updates

We have performed several experiments as proposed in our grant proposal and published/presented the findings in the papers listed.

New funding:
This project has helped generate new data which have been used to apply for an American Heart Association (AHA) Grant-in-Aid award within one year of the commencement of the COBRE project. Dr. Abid received AHA Grant-in-Award in 2014 (2014-2017).

New project:
The findings of the current project led to a better understanding of the subcellular role of ROS, which led to new project direction resulting in generation of novel transgenic mouse model that overexpresses endothelium-specific mitochondrial antioxidant MnSOD (Tg-MnSOD). Preliminary data obtained using this novel animal model with reduced mitochondrial ROS in vascular endothelium have been used to develop an R01 grant application.

Collaboration:
We have ongoing collaboration with Professor of Kaiko Irani, MD (University of Iowa Medical School) and Dr. Christopher Carman (Harvard Medical School) on the role of reactive oxygen species on vascular endothelium.

We have recently initiated collaboration with Professor Peter Wipf (University of Pittsburgh) to study the roles of mitochondria-specific antioxidant in coronary angiogenesis in post-infarct myocardial ischemia.

We have also initiated a very interesting research project with Professor Howard Petty (University of Michigan) to develop therapeutic modalities for coronary angiogenesis using nanoparticle-based oxidants and antioxidants.

Application for NIH R01 grants:

  1. Two R01 Applications have been submitted, one as PI and another as MPI.
Mentors

Frank Sellke, MD
Chief of Cardiothoracic Surgery
Rhode Island Hospital

Elizabeth Harrington, PhD
Associate Dean, Office of Graduate and Postdoctoral Studies
Associate Professor of Medicine (Research), Brown University, Providence VAMC, RI