Zhang Lab

Research Overview

Dr. Zhang has led studies focused on the translational medicine of Alzheimer’s disease. He has investigated molecules of different mechanisms of action for treating AD, including the γ-secretase modulators (GSMs), various natural products (including curcumin and its analogs), small molecule epigenetic and neuroinflammatory regulators, as well as FDA-approved drugs (e.g. cromolyn) that are potentially usable as AD drugs. Additionally, Dr. Zhang has unraveled new AD biomarkers using an array of state-of-the-art technologies, including multiplex biochemical assays, molecular positron emission tomography (PET) imaging—which led to the discovery of a new GSM-based probe enabling the visualization of Alzheimer’s γ-secretase in the brain of live animals and potentially humans—and machine learning-integrated Raman spectrometry screening, among others.

Research Thrusts:

1. Continue investigating molecules of different mechanisms of action for treating AD, including the γ-secretase modulators (GSMs), various natural products (including curcumin and its analogs), small molecule epigenetic and neuroinflammatory regulators (e.g., inhibitors of HDAC6, HDAC11 and NLRP3 neuroinflammasome), and other promising molecules that are potentially usable as AD drugs.
2. Further identification of new AD biomarkers using an array of state-of-the-art technologies, including multiplex biochemical assays, molecular positron emission tomography imaging and machine learning-integrated Raman spectrometry screening, among others.
3. Explore mechanisms of AD etiology, using new research methods and tools (e.g., the use of clinically promising imaging probes).

Lab Members

Martin (Can) Zhang, MD, PhD
Principal Investigator 

Dr. Zhang is an Associate Professor of Neurology and a faculty member of the McCance Center for Brain Health at the Massachusetts General Hospital and Harvard Medical School. Dr. Zhang received his MD and master’s degree at Weifang Medical College in China. He then earned his PhD at Drexel University, followed by a postdoctoral fellowship at Mass General and Harvard Medical School. Funded through research grants from the NIH, ADDF, and the Cure Alzheimer’s Funds, Dr. Zhang is working with a highly collaborative research team and is mentoring trainees through these research projects.

View Dr. Zhang's Harvard Catalyst profile

Fleur Lobo, PhD 
Research Fellow 

Dr. Lobo is originally from Mumbai, India and moved to Los Angeles in 2014 to pursue my Master's and PhD degrees. She graduated with a PhD in Biology of Aging at the University of Southern California where she studied the effects of dietary interventions in mouse models of Alzheimer's and Parkinson's Disease. As a Research Fellow in Dr. Zhang's lab in Dr. Tanzi's unit, Dr. Lobo’s projects involve the characterization of epigenetic modulators that regulate AD pathology. Outside of the lab, Dr. Lobo enjoys ballroom dancing, cooking, photography and painting. 

Prasenjit Mondal, PhD 
Research Fellow 

Dr. Prasenjit Mondal is a Research Fellow of Neurology at Massachusetts General Hospital and the Harvard Medical School. Dr. Mondal received his master’s degree from the Indian Institute of Technology Kanpur, India and his PhD from the Indian Institute of Chemical Biology. In his doctoral research work, Dr. Mondal has developed various platforms, designed peptide/small molecules for the development potential neuroprotective agents in AD therapeutics. Dr. Mondal pursued his postdoctoral work in Dr. Bradley T. Hyman’s laboratory on liquid-liquid phase separation (LLPS) and tau biology in AD at Mass General. He is continuing his post-doctoral research in Dr. Zhang’s laboratory within the larger Genetics and Aging Research Unit at Mass General and Harvard Medical School, studying the role and mechanism of action of various epigenetic and neuroinflammation regulatory proteins in neurodegeneration. Recently, Dr. Mondal has optimized a small molecule inhibitor of epigenetic protein HDAC6 that significantly alleviates the neuropathological symptoms in AD.

Ashley Gomm 
Research Technician

Recent Publications

1. Raven F*, Ward JF*, Zoltowska K, Wan Y, Choi SH, Miller SJ, Shen X, Rynearson K, Berezovska O, Wagner S, Tanzi RE, and Zhang C. Soluble gamma-secretase modulators attenuate Alzheimer’s β-amyloid pathology and induce conformational changes in presenilin 1. *equal contribution. Ebiom; 2017 Oct;24:93-101. PMC5652037
2. Ma C, Su J, Sun Y, Shen N, Feng Y, Li B, Yang X, Wu H, Liang Y, Zhang H, Herrmann A, Tanzi RT, Liu K, and Zhang C. Significant upregulation of Alzheimer’s β-amyloid induced by extracellular elastin polypeptides. Angew Chem Int Ed. 2019 Dec 16;58(51):18703-18709. PMID:31609093. PMC7187254
3. Xu Y, Wang C, Wey H, Liang Y, Chen Z, Choi S, Ran C, Rynearson K, Bernales D, Koegel R, Fiedler S, Striar R, Wagner W, Tanzi RE, and Zhang C. Molecular imaging of Alzheimer’s disease-related gamma-secretase in mice and non-human primates. J Exp Med. PMID: 2020 Dec 07, (217)12. PMC7553790
4. Zhang S, Bai P, Lei D, Liang Y, Zhen S, Bakiasi G, Pang H, Choi SH, Wang C, Tanzi RE, and Zhang C. Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer’s disease-related neuropathology in cell models J Biol Chem. co-corresponding senior author. 2022 Mar 3;101794. doi: 10.1016/j.jbc.2022.101794. PMC8958546
5. Mondal P, Bai P, Gomm A, Bakiasi G, Lin L, Choi SH, Tanzi RE, Wang C, and Zhang C. Structure-based discovery of small molecule inhibitor of histone deacetylase 6 (HDAC6) that significantly reduces Alzheimer’s disease neuropathology. co-corresponding author. Adv Sci 2024 Jan;11(1):e2304545. doi: 10.1002/advs.202304545. PMC10767396

Featured News

Researchers Identify a New Small Molecule Inhibitor for Use Against Alzheimer’s Disease – Mass General Brigham