Chao Ma Laboratory

Research

Overview

Engineering human in vitro models of physiology and diseases for precision medicine  

Precision medicine aims to deliver personalized treatments to any given patient, necessitating an elucidation of the patient’s genetic makeup and the disease microenvironment. To obtain such an understanding, experimental models that recapitulate human physiology and pathophysiology are highly needed, yet largely unavailable. The central goal of our work is to engineer and apply microfluidic organs-on-chips to first recreate in vitro tissue/disease models; then to unravel the mechanisms underlying tissue homeostasis, disease progression, and treatment resistance; and finally, to screen therapeutic potential of novel treatments. Our research provides a blueprint for the development and leverage of tissue-engineered humanized in vitro platforms, which may enable a novel paradigm for drug discovery, development, and evaluation in a physiologically relevant context. 

1. Cancer Bioengineering

Understanding the crosstalk between tumor and neighboring cells in the tumor microenvironment is indispensable for optimal therapy. 

Project goals:

• Establishing a line of novel microfluidic-based microphysiological systems
• Reconstituting the in vivo pathology of diverse tumor niches
• Screening optimal chemotherapy and/or immunotherapy 

2. Liver Engineering

The liver is a complex hierarchical organ in which several types of cells self-assemble into fine-tuned structures that perform functions including metabolism, detoxification, and synthesis. 

Project goals:

• Development of bioinspired strategies to fabricate liver blocks
• High-throughput and advanced liver organ manufacturing
• Liver disease modeling and therapeutics testing

3. Integrated Single-Cell Analysis

Single-cell analysis measures molecular signals such as transcription, translation, and regulation within a single cell, providing a new perspective for cell physiology and pathological processes, drug screening, and early diagnosis. 

Project goals:

• Microfluidic manipulation of single cells
• T/B cell-based therapy testing
• Antibody-secreting hybridoma screening

Selected Publications

Ma C, Wang H, Liu L, Tong J, Witkowski MT, Aifantis I, Ghassemi S, Chen W. A bioengineered immunocompetent human leukemia chip for preclinical screening of CAR T cell immunotherapy. Res Sq [Preprint]. 2023 Apr 21:rs.3.rs-2762929.

Liu L, Ma C, Zhang Z, Witkowski MT, Aifantis I, Ghassemi S, Chen W. Computational model of CAR T-cell immunotherapy dissects and predicts leukemia patient responses at remission, resistance, and relapse. J Immunother Cancer. 2022 Dec;10(12):e005360.

Ma C, Peng Y, Li H, Chen W. Organ-on-a-Chip: A New Paradigm for Drug Development. Trends Pharmacol Sci. 2021 Feb;42(2):119-133.

Ma C, Witkowski MT, Harris J, Dolgalev I, Sreeram S, Qian W, Tong J, Chen X, Aifantis I, Chen W. Leukemia-on-a-chip: Dissecting the chemoresistance mechanisms in B cell acute lymphoblastic leukemia bone marrow niche. Sci Adv. 2020 Oct 30;6(44):eaba5536.

Witkowski MT, Dolgalev I, Evensen NA, Ma C, Chambers T, Roberts KG, Sreeram S, Dai Y, Tikhonova AN, Lasry A, Qu C, Pei D, Cheng C, Robbins GA, Pierro J, Selvaraj S, Mezzano V, Daves M, Lupo PJ, Scheurer ME, Loomis CA, Mullighan CG, Chen W, Rabin KR, Tsirigos A, Carroll WL, Aifantis I. Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2020 Jun 8;37(6):867-882.e12.