Jamila H Siamwala, Ph D is an Assistant Professor of Molecular Pharmacology, Physiology and Biotechnology at Brown University and an affiliate at Providence VA Medical Center. She is a graduate of Anna University, Chennai where she received her training in angiogenesis and stem cell differentiation. She has trained in mitochondrial physiology as a post-doctoral fellow in University of California San Diego and moved to Brown University as a research associate in December 2017. She became an Assistant Professor in February 2019.
Dr. Siamwala is a vascular cell physiologist by training and is interested in mitochondrial functions, metabolome, immune interactions and immune based therapies for cardiovascular and neurovascular diseases. She led the group investigating the mitochondrial functions of space and ground astronaut’s plasma components on skeletal muscle cells in the historic NASA twins study published in Science journal.
Dr. Siamwala is currently investigating the role of macrophage mechanisms in right ventricular fibrosis and pulmonary hypertension. Her work is supported by grants from NIGMS CardioPulmonary Vascular Biology Center for Biomedical Research Excellence (COBRE CPVB), Rhode Island Foundation and National Institute of Aging. She is also a recipient of two summer 2019 UTRA awards.
Dr. Siamwala serves on NASA grant review panel and is a reviewer of Scientific reports, British Journal of Pharmacology and American Journal of Physiology-Regulative, Integrative and Comparative Physiology.
Dr. Siamwala received the Young Scientist Award, Annual meeting of Society for Free Radical Research (SFRR) in 2011 and EEP National Space Biomedical Research Institute’s Gravitational Physiology Beginning Investigator Award from the American Physiology Society in 2015.
Pulmonary arterial hypertension (PAH) is a devastating syndrome associated with vasoconstriction and pulmonary vascular remodeling, resulting in increased right ventricular (RV) afterload and RV hypertrophy. Therapies such as prostacyclins, calcium channel blockers, endothelin receptor blockers, phosphodiesterase inhibitors and guanylate cyclase stimulators for vascular management of PAH exists however none exists for the failing RV. Cardiac fibroblasts (CF’s) are the predominant cell type contributing to increased interstitial, perivascular fibrosis and abnormal accumulation of fibrillary collagen in the heart. However, little is known about the mechanisms of CF’s proliferation and consequent RV fibrosis and failure. Pro-inflammatory cytokines secreted by the macrophages specifically, IL-1 β are associated with adverse RV modelling and mortality in animal and humans with PAH. Our preliminary data suggests that conditioned media from the primary macrophages increases primary CF proliferation. Moreover, the IL-1β levels in the RV from pulmonary artery banded animals (PAB) is higher compared to sham surgery mice. The goal of this pilot study is to investigate the inflammatory processes of RV fibrosis to develop immune based therapy for improving RV systolic and diastolic function in PAH. We will employ unique macrophage specific IL-1β knockout and periostin (myofibroblast specific) IL-1R knockout pulmonary artery banded mice model of PAH to evaluate if IL-1β inhibition will prevent RV fibrosis and RV dysfunction. The hypothesis is that RV pressure overload in PAH leads to macrophage IL-1β-dependent fibrosis through cardiac fibroblast IL-1R signaling with consequent fibroblast proliferation and collagen deposition. The macrophage cell specific inducible IL-1β knockout mice model subjected to pulmonary artery banding (PAB) will be used to demonstrate the dependence of RV fibrosis on macrophage IL-1β expression. A second unique periostin specific IL-1R knockout mice subjected to PAB will be used to demonstrate the dependence of RV fibrosis on cardiac fibroblast IL-1R signaling. Finally, an FDA approved IL-1β blocker Anakinra will be employed to validate IL-1 receptor antagonist therapy as a viable clinical strategy for preventing RV failure in a rat model of PAH.
waiting for contents
Elizabeth Harrington, PhD
Associate Dean for Graduate and Postdoctoral Studies in the Division of Biology and Medicine, Professor of Medicine\
Sharon Rounds, MD
Associate Dean for Clinical Affairs, Professor of Medicine, Professor of Pathology and Laboratory Medicine Brown University
Funding Source: COBRE CPVB PILOT PROJECT
Title: “Right ventricular fibrosis from pulmonary arterial hypertension is dependent on macrophage IL-1B signaling”
Project period: 2/1/2019 – 2/1/2020
Funding Source: Rhode Island Foundation
Title: “Macrophages under pressure in right ventricular dysfunction associated with pulmonary arterial hypertension”
Project period: 03/01/2019 to 02/28/2020
Funding Agency: NIGMS administrative supplement
Title: “Neurovascular Aging Phenotypes of Alzheimer’s and Progeria: Focus on Inflammation and Blood Brain Barrier”
Project period: 06/01/2019 to 05/30/2020
Ocean State Research Institute
Providence VA Medical Center
830 Chalkstone Avenue
Providence RI 02908
Research Funded by
Research reported in this website was supported by the National Institute of General Medical Science of the National Institutes of Health under grant number P20GM103652.