The Brody Lab

The University of Michigan

The Brody lab is broadly focused on the molecular signals that underlie cardiac disease onset and progression. We have a specific interest in understanding how intracellular signaling is compartmentalized and regionally controlled by lipid modifications that modulate the function of signaling molecules in various cell types of the heart to control cardiac physiology and pathogenesis. Our laboratory utilizes a combination of mouse genetics, biochemistry, and molecular and chemical biology techniques to gain insight into pathophysiological signaling mechanisms that contribute to human cardiovascular disease.

Research

One area the Brody lab is actively investigating is how the DHHC family of S-acyl transferase enzymes control signaling through lipid modifications. Our work has shown that DHHC3 transferase activity at the cardiomyocyte Golgi apparatus is a nodal point for reactive signaling in the heart including functioning as a key regulator of signaling by the Rho family of small GTPases with profound effects on cardiac remodeling and failure. We have a broad interest in signaling mediated by G-protein-coupled receptors and small GTPases in the context of cardiac disease. We are using transgenic and gene-targeted mouse models and cellular, molecular, and biochemical studies to elucidate how DHHC enzymes regulate signaling molecules in the heart and determine how specific lipid modifications alter protein function to control cardiac physiology and disease.

Publications

Brody MJ, Vanhoutte D, Bakshi CV, Liu R, Correll RN, Sargent MA, and Molkentin JD. Disruption of valosin-containing protein activity causes cardiomyopathy and reveals pleiotropic functions in cardiac homeostasis. J Biol Chem, 294(22):8918-8929, 2019.

Khalil H, Kanisicak O, Vagnozzi RJ, Johanesn AK, Maliken BD, Prasad V, Boyer JG, Brody MJ, Schips TG, Kilian KK, Correll RN, Kawasaki K, Nagata K, and Molkentin JD. Cell-specific ablation of Hsp47 defines collagen producing cells in the injured heart. JCI Insight, 4(15):128722, 2019.

Schips TG, Vanhoutte D, Vo A, Correll RN, Brody MJ, Khalil H, Karch J, Tjondrokoesoemo A, Sargent MA, Maillet M, Ross RS, Molkentin JD. Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability. Nat Commun, 10(1):76, 2019.

Brody MJ, Vanhoutte D, Schips TG, Boyer JG, Bakshi CV, Sargent MA, York AJ, and Molkentin JD. Defective Flux of Thrombospondin-4 through the Secretory Pathway Impairs Cardiomyocyte Membrane Stability and Causes Cardiomyopathy. Mol Cell Biol, 38(14), 2018.
~selected for the cover photo and chosen as a Spotlight article by the Editor

Karch J, Schips TG, Maliken BD, Brody MJ, Sargent MA, Kanisicak O, and Molkentin JD. Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. ELife, 6:30543, 2017.

Brody MJ, Schips TG, Vanhoutte D, Kanisicak O, Karch J, Maliken BD, Blair NS, Sargent MA, Prasad V and Molkentin JD. Dissection of Thrombospondin-4 domains involved in Intracellular Adaptive Endoplasmic Reticulum Stress-Responsive Signaling. Mol Cell Biol, 36(1):2-12, 2016.

Vanhoutte D, Schips TG, Kwong JQ, Davis J, Tjondrokoesoemo A, Brody MJ, Sargent MA, Kanisicak O, Rabinowitz JE, Volk T, McNally EM, and Molkentin JD. Thrombospondin expression in myofibers stabilizes muscle membranes. ELife, 5:17589, 2016.

Brody MJ and Lee Y. The role of Leucine-rich repeat containing protein 10 (LRRC10) in dilated cardiomyopathy. Front Physiol, 7(337):1-6, 2016.

Brody MJ, Feng L, Grimes AC, Hacker TA, Olson TM, Kamp TJ, Balijepalli RC, Lee Y. LRRC10 is required to maintain cardiac function in response to pressure overload. Am J Physiol Heart Circ Physiol, 310(2):H269-78, 2016.

Kanisicak O, Khalil H, Ivey MJ, Karch J, Maliken BD, Correll RN, Brody MJ, J Lin SC, Aronow BJ, Tallquist MD, Molkentin JD. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun, 7:12260, 2016.

Karch J, Kanisicak O, Brody MJ, Sargent MA, Michael DM, Molkentin JD. Necroptosis Interfaces with MOMP and the MPTP in Mediating Cell Death. PLoS One, 10(6):e0130520, 2015.

Brody MJ, Cho E, Mysliwiec MR, Kim T, Carlson CD, Lee K, and Lee Y. Lrrc10 is a novel cardiac-specific target gene of Nkx2-5 and GATA4. J Mol Cell Cardiol, 62: 237-246, 2013.

Brody MJ, Hacker TA, Patel JR, Feng L, Sadoshima J, Tevosian SG, Balijepalli RC, Moss RL, and Lee Y. Ablation of the cardiac-specific gene Leucine-rich repeat containing 10 (Lrrc10) results in dilated cardiomyopathy. PLoS One, 7(12):e51621, 2012.

Rufer ES, Hacker TA, Flentke GR, Drake VJ, Brody MJ, Lough J, Smith SM. Altered cardiac function and ventricular septal defect in avian embryos exposed to low-dose trichloroethylene. Toxicol Sci, 113(2):444-52, 2010.

Lab Members

Matt Brody, PhD

Assistant Professor

Kumar Subramani, MS

Lab Manager

Kobina Essandoh, PhD

Postdoctoral Fellow

Bharat Koripella

Undergraduate Student

Hannah Makki

Undergraduate Student

Alexa Tarui

Undergraduate Student

Join the Team!

Postdoctoral Fellows
We are recruiting motivated biochemists and molecular, cellular, and cardiac biologists with interest in research in the Brody lab. Contact Matt at majbrody@umich.edu

Graduate Students
We are looking for graduate students passionate about biomedical research to join the lab. We accept students from PhD programs in Pharmacology and Cellular and Molecular Biology through the Program in Biomedical Sciences (PIBS) of the University of Michigan Medical School as well as the University of Michigan Program in Chemical Biology.

Undergraduates
Driven undergraduate students with an interest in molecular and cellular cardiology research should contact Matt at majbrody@umich.edu.

News

Matt won the American Heart Association Katz Young Investigator Award

We presented our work at the FASEB meeting on Protein Lipidation

Kobi won a travel award from ASBMB to present his work on zDHHC9-regulated signaling in the heart at EB2020 in San Diego!

Contact

Matt Brody, PhD
Assistant Professor
Department of Pharmacology
Department of Internal Medicine
University of Michigan Medical School

majbrody@umich.edu

734-763-3255

Lab

1240 MSRBIII
1150 W. Medical Center Dr.
Ann Arbor, MI 48109-5632

734-647-8807