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 strong 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. We utilize 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 we are actively investigating is how the zDHHC family of S-acyl transferase enzymes control signaling in cardiac cells. We found palmitoylation of signaling proteins catalyzed by some of these enzymes at the surface of the cardiomyocyte Golgi membrane functions as a critical mechanism governing cardiac stress adaptation and remodeling, including instrumental roles in regulation of exocytosis and natriuretic peptide release, cytokine receptor signaling, and myocardial oxidative stress. We have a broader interest in identifying and elucidating pharmacological strategies to inhibit intracellular signaling pathways that promote cardiac hypertrophy and failure.

Publications

Essandoh K, Subramani A, Ferro OA, Teuber JB, Koripella S, and Brody MJ. zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion through Palmitoylation of Rab3gap1. JACC Basic Transl Sci, 2023. https://doi.org/10.1016/j.jacbts.2022.11.003

Teuber JP, Essandoh K, Hummel SL, Madamanchi NR, Brody MJ. NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction. Antioxidants, 11(9):1822, 2022.

Guo AH, Baliira R, Skinner ME, Kumar S, Andren A, Zhang L, Goldsmith RS, Michan S, Davis NJ, Maccani MW, Day SM, Sinclair DA, Brody MJ, Lyssiotis CA, Stein AB, Lombard DB. Sirtuin 5 levels are limiting in preserving cardiac function and suppressing fibrosis in response to pressure overload. Sci Rep, 12(1):12258, 2022.

Essandoh K, Auchus RJ, and Brody MJ. Cardiac decompensation and promiscuous prenylation of small GTPases in cardiomyocytes in response to local mevalonate pathway disruption. J Pathol, 256(3):249-252, 2022.

Vanhoutte D, Schips TG, Vo A, Grimes KM, Baldwin TA, Brody MJ, Accornero F, Sargent MA, Molkentin JD. Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy. Nat Commun, 12(1):3928, 2021.

Essandoh K, Philippe JM, Jenkins PM, and Brody MJ. Palmitoylation: A Fatty Regulator of Myocardial Electrophysiology. Front Physiol, 11(108):1-11, 2020.

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.

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/Research Specialist Senior

Kobina Essandoh, PhD

Postdoctoral Fellow

Rob Goldsmith, BS

Pharmacology PhD Candidate

James Teuber, BS

Pharmacology PhD Student

Hitarthi Vyas, PhD

Postdoctoral Fellow

Bharat Koripella

Undergraduate Student

Sneha Dinda

Undergraduate Student

Rachel Scissors

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

Kobi’s research article “zDHHC9 Regulates Cardiomyocyte Rab3a Activity and Atrial Natriuretic Peptide Secretion through Palmitoylation of Rab3gap1” was accepted for publication in JACC: Basic to Translational Science!

James and Kobi’s review article “NADPH Oxidases in Diastolic Dysfunction and Heart Failure with Preserved Ejection Fraction” was published in Antioxidants!

James and Kobi won the Graduate Student and Postgraduate Shaomeng Wang and Ju-Yun Li Pharmacology Research Awards, respectively, at the Departmental Retreat at Maumee Bay! (09/2022)

James was awarded a National Research Service Award F31 fellowship to investigate functions of Rac1 palmitoylation in cardiac hypertrophy and oxidative stress! (01/2023-12/2025)

Olivia successfully defended their Masters thesis “Using Click Chemistry to Investigate Palmitoylation of Jak1 and Rab3gap1 by zDHHC S-Acyltransferases” and started as a Research Scientist at Glaukos Corporation! (07/2022)

Kobi won a New Investigator Travel Award at the American Heart Association Basic Cardiovascular Sciences Meeting in Chicago! (07/2022)

Kobi was selected for an oral presentation and won Best Poster Award for his research on palmitoylation-dependent regulation of atrial natriuretic peptide secretion at the Cardiac Regulatory Mechanisms Gordon Conference in New London, NH (06/2022)!

James was selected for an oral presentation of his research on Rac1 palmitoylation in myocardial hypertrophy and oxidative stress at the Midwestern Pharmacology Colloquium at Wayne State University in Detroit, MI (06/2022)

Kobi, Rob, and James all have AHA fellowships to support their research!!! Thanks to the AHA for supporting our research and careers!

Other News

Our editorial “Cardiac decompensation and promiscuous prenylation of small GTPases in cardiomyocytes in response to local mevalonate pathway disruption” in collaboration with Rich Auchus was published in the Journal of Pathology.
Our co-authored research article “Sirtuin 5 levels are limiting in preserving cardiac function and suppressing fibrosis in response to pressure overload” with the David Lombard lab was published in Scientific Reports (06/2022)
James was awarded an AHA Pre-doctoral Fellowship to investigate functions of Rac1 palmitoylation in cardiac hypertrophy and oxidative stress! (01/2022-12/2023)
Kumar was promoted to Lab Specialist Senior! Congrats! (09/2021)
Kobi was awarded an AHA Post-doctoral Fellowship to investigate functions of zDHHC9 in hypertrophic signaling in the heart! (4/2021-03/2023)
Rob was awarded an AHA Pre-doctoral Fellowship to investigate functions of zDHHC3 in fibroblast signaling and cardiac fibrosis! (04/2021-03/2023)
Kobi won a travel award from ASBMB to present his work on zDHHC9-regulated signaling in the heart at EB2021.
Kobi was awarded the Department of Pharmacology Upjohn Postdoctoral Fellowship Award! (06/2020-05/2022)

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