Chemical Biology and Molecular Medicine

The Chemical Biology and Molecular Medicine (CBMM) Program integrates chemical biology and systems biology technologies to develop new therapeutic approaches for the treatment of cancer. Along with research in chemistry and drug discovery and clinical trials, the CBMM includes members interrogating signaling pathways that regulate cell proliferation and survival to identify new targets for cancer therapeutics. Inclusion of basic scientists, chemists, and clinical researchers creates unique opportunities to rapidly translate novel strategies into the clinic, while conversely also increasing the flow of observations from the clinic back to the laboratory for mechanistic testing. 

CBMM members have had a major impact on discerning mechanisms of drug resistance, identifying new vulnerabilities for cancer, developing new small molecules for cancer therapy, and testing new therapeutic and biomarker strategies in early-phase clinical trials. Continued success in these areas, as well as progress in new initiatives, is informed by the Program Specific Aims:

Aim 1: Identify, validate, and characterize targets with therapeutic relevance in refractory and metastatic malignancies.
CBMM, with support from MCC Shared Resources, uses system-level unbiased mass spectrometry- and genomics-based approaches, specifically proteomics, proteogenomics, and proteo-activity analyses, as well as novel targeted approaches such as proximity ligation analyses and chemical proteomics, as tools for assessing signaling circuits and for target discovery. These approaches are used to define: (i) mechanisms of acquired resistance in refractory cancers; and (ii) new therapeutic strategies for treating patients afflicted with these malignancies.

Aim 2: Design small molecule chemical probes to modulate oncogenic targets and pathways.
CBMM members have designed and developed several novel single- and dual-targeting small molecule therapeutics. Their goals are to develop new single- and dual-targeting small molecule therapeutics using novel chemical probes, solving drug-target structures with x-ray crystallography and structure-based drug design. For new targets identified in the discovery campaigns of Aim 1, CBMM members also screen small molecule chemical libraries to identify new leads, using reiterative hit-to-lead medicinal chemistry optimization and crystallography to generate potent and safe leads that have desired drug-like properties.

Aim 3: Develop and implement mechanism-based therapeutic trials.
New targeted therapeutic strategies and new CBMM-generated anti-cancer agents are moved into mechanism-based clinical trials in hematological malignancies, melanoma, lung cancer and GI malignancies. Genomic and proteomic technologies are used to enrich patient enrollment to targeted agent clinical trials, study drug mechanisms of action within tumor tissues, and study the process of drug resistance. Novel small molecule therapies developed in CBMM are tested first in human studies; next, rational combination therapies informed by CBMM pre-clinical science that thwart drug resistance are directly tested in patients for tolerability and early signals of activity. Imaging-based biomarker approaches are developed by converting biomedical images into mineable data to help guide prognosis, prediction, and therapeutic monitoring.

Program Leaders:
Eric B. Haura, MD
Saïd Sebti, PhD

Members:
Khaldoun Almhanna, MD, MPH
Melissa Alsina, MD
Rachid Baz, MD
Julio Jiminez Chavez, MD 
Dung-Tsa Chen, PhD
Alberto A. Chiappori, MD
Christine H. Chung, MD
Domenico Coppola, MD
William S. Dalton, PhD, MD
Juan R. Del Valle, PhD
Steven Allen Eschrich, PhD
Robert J. Gillies, PhD
Jhanelle Gray, MD
Eric B. Haura, MD
Haitao (Mark) Ji, PhD
Richard Kim, MD
Rami S. Komrokji, MD
John M. Koomen, PhD
Jeffrey E. Lancet, MD
Eric K. Lau, PhD
Nicholas James Lawrence, PhD
Alan F. List, MD
Kiran Mahajan, PhD
Nupam P. Mahajan, PhD
Mokenge P. Malafa, MD
David L. Morse, PhD
Taiga Nishihori, MD
Eric Padron, MD
Damon Reed, MD
Uwe Rix, PhD
Jeffery Russell, MD, PhD
Solmaz Sahebjam, MD
Michael J. Schell, PhD
Ernst Schonbrunn, PhD
Said M. Sebti, PhD
Kenneth H. Shain, MD, PhD
Keiran S. Smalley, PhD
Gregory M. Springett, MD, PhD
Jonathan R. Strosberg, MD
Daniel Sullivan, MD
Kenneth Tsai, MD, PhD
Lixin Wan, PhD
Robert M. Wenham, MD, MS, FACOG, FACS
Jingsong Zhang, MD, PhD