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Dissertation Defense: Extracellular Matrix Contributions to Early Vascular Development and Pericyte Precursor Dynamics

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Maruf Hoque

Dissertation Defense: Extracellular Matrix Contributions to Early Vascular Development and Pericyte Precursor Dynamics

Maruf M. Hoque

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Chappell Lab, Fralin Biomedical Research Institute at VTC
May 9, 2023 at 11:30 a.m.,  Room R3012, 2 Riverside Circle

About this Dissertation

The vasculature is a highly intricate system of “highways” that shuttles blood from the heart to every tissue and organ in the human body. These vessels are responsible for carrying oxygen, trafficking hormones, delivering nutrients, and removing waste products from the body. The formation of a functioning vascular system depends on the close coordination of many cell types and, on the capillary level, specifically endothelial cells and pericytes as well as the surrounding protein microenvironment, known as the extracellular matrix (ECM). Impaired coordination amongst the cellular and protein constituents results in the improper functioning of the vascular network and can eventually contribute to the failure of organ systems. This dissertation research focuses on how improper ECM deposition affects vascular assembly. Hoque, working in the Chappell lab, utilized several approaches to affect ECM composition, specifically: 1) hypoxia exposure, 2) reducing ECM pharmacologically and 3) utilizing lentiviral-mediated silencing of Type IV Collagen (Col-IV, gene Col4a1) expression. In these experimental settings, we observed downstream changes in the coordination between endothelial cells and pericytes while forming vascular networks. In short, this dissertation work suggests that excess ECM deposition, and particularly that of Col-IV, has unique deleterious effects on the developing vasculature as compared to reduced ECM deposition. The findings from this work suggest mechanisms underlying how the vasculature may be destabilized in hypoxia-associated pathologies, such as preeclampsia.

More About the Candidate and Project

Education

Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate

Georgia State University, M.S., Biology

Georgia State University, B.S., Biology and Neuroscience

Training

Graduate Research Assistant, Chappell Lab, Fralin Biomedical Research Institute at VTC

Mentor

John Chappell, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC

Committee Members

  • Jennifer Munson, Ph.D., Associate Professor, Fralin Biomedical Research Institute at VTC
  • Michelle Theus, Ph.D.,  Associate Professor, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine; Co-director, TBMH program; Director, Center for Neurotrama Research
  • Robert Gourdie, Ph.D., FAHA, AIMBE, Commonwealth Research Commercialization Fund Eminent Scholar in Heart Reparative Medicine Research, Director, Center for Vascular and Heart Research, Fralin Biomedical Research Institute at VTC
  • Biraj Patel, M.D., Associate Professor, Virginia Tech Carilion School of Medicine
  • Aspire Aware, Virginia Tech Division of Student Affairs, 2022
  • Zweifach Graduate Student Travel Award, Microcirculatory Society, 2021
  • UVA Policy Bootcamp Certificate, 2021
Publications

Hoque MM, Barnes A, Chappell JC. Excess Type IV Collagen Contributes to Defective Early-Stage Vessel Formation during Prolonged Hypoxia. In preparation for submission to Developmental Dynamics.

Payne LB, Abdelazim H, Hoque MM, et al. A Soluble Platelet-Derived Growth Factor Receptor-β Originates via
Pre-mRNA Splicing in the Healthy Brain and is Up-regulated during Hypoxia and Aging. Biomolecules. Accepted April 2023.

Hoque MM, Abdelazim H, Jenkins-Houk C, Wright D, Patel B, Chappell JC. The cerebral microvasculature: Basic and clinical perspectives on stroke and glioma. Microcirculation. 2020 Nov 10;312671 [Epub ahead of print]. PMID: 33171539; DOI: 10.1111/micc.12671.

Payne LB, Hoque MM, Houk C, Darden J, Chappell JC. Pericytes in Vascular Development. Curr Tissue Microenviron Rep. 2020 Sep;1(3):143-54. Epub 2020 Jul 2. DOI: 10.1007/s43152-020-00014-9

Presentations

Hoque M, et al. Hypoxia Mediated Extracellular Matrix Destabilization impairs pericyte differentiation. Center for Vascular and Heart Retreat. Poster Presentation. (2022)

Hoque M, et al. Pericyte Recruitment Impaired by Hypoxia Mediated Extra Cellular Matrix Destabilization. Vascular Biology. Short Talk and Poster Presentation. (2021)

Hoque M, et al. Collagen-III: an Index of Vascular Maintenance. American Heart Association-Vascular Discovery. Poster Presentation. (2021)

Hoque M, et al. Collagen-III: an indicator for early pericyte differentiation. Poster Presentation. Vasculata. (2021)

Hoque M, et al. Interstitial Col-IV: A template for pericyte recruitment. Short Talk and Poster Presentation. Experimental Biology. (2021)

  • Our Future is Science-Aspen Institute & Coda Societies | 2022-2023 | Mentor
  • Graduate Assistantship Support Task Force | 2022-2023 | Member
  • Peer Mentor for Translational Biology, Medicine & Health | 2019-2022
  • Biomedical Professional Development Symposium | 2022 | Chair/Moderator
  • Graduate/Professional Student Senate at Virginia Tech | 2021-2022 | Past-President            
  • Graduate/Professional Student Senate at Virginia Tech | 2020-2021 | President          
  • Order of the Gavel | 2020-2021 | Member
  • Graduate/Professional Student Senate at Virginia Tech | 2019-2020 | Director of Finance
  • Degree Requirements, Criteria, & Academic Progress Committee | 2020-2022 | Delegate
  • Commission of Graduate & Professional Studies & Policies | 2019-2022 | Delegate      
  • President’s Committee on Governance | 2020-2021 | Member            
  • Task Force on the Future of Student Governance | 2020-2021 | Member
  • President’s Advisory Council | 2020-2021 | Member 
  • Fralin Commercialization Fellow’s Program | 2020 
  • Commission of Student Affairs | 2019-2020 | Delegate 
  • University Council of Strategic Planning and Budgeting | 2019-2020 | Member