Email

jfmartin@bcm.edu

Positions

Vice Chairman/Professor

Molecular Physiology and Biophysics
Baylor College of Medicine
Houston, TX US

Vivian L. Smith Chair in Regenerative Medicine

Baylor College of Medicine
Houston, Texas United States

Director

Cardiomyocyte Renewal Laboratory
Texas Heart Institute
Houston, Texas United States

Education

Postdoctoral Fellowship at University Of Texas MD Anderson Cancer Center

Houston, Texas United States

PhD from University Of Texas Health Science Center

Houston, Texas United States

Clinical Fellowship at University Of Texas Medical School At Houston

Houston, Texas United States

MD from University Of Texas Medical School At Houston

Houston, Texas United States

BS from Fordham University

Bronx, New York United States

Professional Interests

• Cell and Developmental Biology
• Molecular Biology and Genetics
• Human Disease
• Cardiovascular Sciences
• Regenerative Medicine

Professional Statement

For more information about our lab, please visit: https://www.jfmartinlab.com/

We are interested in understanding how developmental pathways are connected to adult tissue regeneration. We are investigating the Hippo, Wnt, and Bmp-signaling pathways for developmental and regenerative capabilities. Our goal is to obtain an in depth understanding of these pathways in order to develop ways to regenerate heart muscle and craniofacial bone. We first reported a role for the Hippo pathway in inhibiting cardiomyocyte proliferation to limit heart size during mammalian development. Our lab also observed that inactivation of Hippo in adult cardiomyocytes unleashes productive heart regeneration and promotes reversal of heart failure and that Hippo functions as a key regulator in cardiac fibroblasts and inflammatory responses. Our ongoing studies are aimed at translating this work into meaningful cardiac therapy approaches.

Limited endogenous adult cardiomyocyte regenerative potential after acute damage results from inadequate adult cardiomyocyte proliferative capacity. Strikingly, the mammalian heart endogenously replaces merely 1% of cardiomyocytes per year. In our previous work, deletion of the Hippo component Sav in adult mouse and pig cardiomyocytes with established ischemic cardiomyopathy and heart failure (HF), results in reversal of HF and improved heart function due to cardiac growth gene activation. We work extensively with ischemia-reperfusion–induced myocardial infarction mouse and pig models and recently demonstrated that locally delivered gene therapy to inhibit Hippo in border zone cardiomyocytes is the first example of bona fide tissue renewal therapy.

In addition, we have made fundamental insights into the role of the transcription factor Pitx2 in atrial fibrillation, the most common sustained arrhythmia in the human population. We made use of the mouse model to investigate Pitx2 in atrial homeostasis but also in left right asymmetric morphogenesis that is essential for human development. Our studies investigating Pitx2 function in craniofacial development have provided insight into the molecular basis of Rieger syndrome. In addition, we uncovered a key function for Bmp signaling in endothelial-mesenchymal transition and cardiac valve development. Our earlier studies uncovered a novel role for canonical Wnt signaling in cardiac progenitor cell diversification and we discovered the first microRNA (miR-17-92) implicated in orofacial clefting. We also have a long-term interest in studying transcription factors involved in cell fate transitions in development and regeneration. Our lab has extensively studied transcription factors, initially using mouse models and reporter alleles, which include paired-related homeobox genes.

Over the past seven years, we have transitioned into single-cell biology and computational biology and have published several high impact papers that address an array of important biologic questions by using single-cell multi-omics approaches. The spatial aspects of neonatal mammalian heart regeneration remain poorly understood. Although previous studies suggest that regeneration activates hundreds of genes, triggers paracrine signaling, and recruits inflammatory cells that presumably colocalize with specific cell-types near the injured site in neonatal heart, we have not achieved an unbiased, spatial and transcriptome-scale understanding of heart regeneration mechanisms. We are therefore employing spatial transcriptomics (ST) to identify the spatially resolved gene regulatory networks (SpGRNs) of genes that become active and the locations where the multiple cell-types colocalize in post-injury hearts. ST is an emerging technology that captures gene expression from intact tissue sections into spatially resolved spots and is a significant advance over single-cell transcriptomics, which loses spatial information of cells. Combining our expertise in machine learning, ST data modeling, and mouse genetics, we deliver a suite of spatial machine learning methods to uncover unknown mechanisms of heart regeneration with the aim of transforming human heart failure therapies. The methods will be broadly applicable to find actionable hypotheses from spatially resolved transcriptomic data generated by any technology. Our methods will also apply to any spatially resolved gene expression dataset from other tissues, such as the brain, fetus, and tumors, where a systematic understanding of the spatially resolved gene regulatory networks and spatial organization of cell-types is essential.

Websites

Selected Publications

• For more information about our lab, please visit "https://www.jfmartinlab.com/." :
• Liu S, Li K, Wagner Florencio L, Tang L, Heallen TR, Leach JP, Wang Y, Grisanti F, Willerson JT, Perin EC, Zhang S, and Martin JF "Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction." Sci Transl Med. 2021 June 30; 13 (600): eabd6892. Pubmed PMID: 34193613
• Leach JP, Heallen TR, Zhang M, Hill MC, Rahmani M, Willerson JT, and Martin JF "Hippo Pathway Deletion Reverses Systolic Heart Failure Post Infarction." Nature. 2017 October 12; 550 (7675): 260-264. Pubmed PMID: 28976966
• Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF "Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size.." Science. 2011 April 22; 332 (6028): 458-61. Pubmed PMID: 21512031

Funding

"Early Detection of Cardiac Allograft Vasculopathy in Post-transplant Pediatric Hearts via Single-cell Genomics" - #824138

(07/01/2021 - 06/30/2024) Grant funding from AHA/EH Research Awards in Pediatric Heart Transplantation

“Pitx2 in atrial fibrillation” - #R01 HL118761

(04/01/2014 - 01/31/2026) Grant funding from NIH/NHLBI

“Hippo and Wnt signaling in cardiac regeneration" - #R01 HL127717

(01/01/2016 - 12/31/2023) Grant funding from NIH/NHLBI