Chi Li, Ph.D.

Education:

B.S., Biology, University of Science and Technology of China, Hefei, China, 1991
M.A. & M.Phil., Molecular Biology, Columbia University, New York City, NY, 1995
Ph.D., Molecular Biology, Columbia University, New York City, NY, 1998
Postdoctoral Fellowship, University of Pennsylvania Cancer Center, Philadelphia, PA, 2006

Curriculum Vitae

Current Positions:

Assistant Professor, Department of Medicine, University of Louisville School of Medicine
Member, James Graham Brown Cancer Center
Associate Member, Department of Pharmacology and Toxicology, University of Louisville School of Medicine

Contact Information:

Clinical Translational Research Building, Room 418
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone 502-852-0600

Fax 502-852-3661

Email: chi.li@louisville.edu

Research Description:

Dr. Li’s laboratory studies genetic mutations involved in the initiation and development of tumors, particularly those regulating the timing and process of cell death.  Many tumor cells are abnormally resistant to programmed cell death (apoptosis), causing uncontrolled growth of cancer.  A major challenge in cancer research is to discover novel drugs that thwart the resistance displayed by tumor cells due to impaired apoptotic pathways.  Thus, restoring the aberrant apoptotic signaling in tumor cells might render them more susceptible to stress conditions and subsequent cell death.  The Li laboratory focuses on exploring novel strategies for cancer therapy by activating the apoptosis pathways directly in tumor cells, which could potentially lead to the development of new anti-tumor drugs.

The Li group has discovered several novel molecules that preferentially trigger tumor cell apoptosis in tumors.  For instance, we have identified a small molecule that induces apoptosis by changing the conformation of the pro-apoptotic Bcl-2 protein Bax and subsequently activating Bax in tumor cells.  This molecule might represent a lead compound of novel therapeutic drugs that preferentially induce apoptosis in tumors.

Recently, Dr. Li’s laboratory has been collaborating with Dr. Yaddanapudi’s laboratory and Dr. Eaton’s laboratory at the James Graham Brown Cancer Center to explore the potential of exosomes derived from embryonic stem cells (ESCs) as a prophylactic vaccine for lung cancer.  We have successfully generated a prophylactic vaccine comprised of exosomes derived from ESCs engineered to produce the immune-stimulatory factor GM-CSF.  Vaccination of mice with these exosomes significantly slows or blocks the outgrowth of implanted lung tumors by promoting immune responses.  We believe that a similar vaccine derived from human ESCs expressing GM-CSF may be applicable to humans with increased risk of developing cancer.

Representative Publications:

Anti-tumor activity of a homeoserine lactone

  1. Schwarzer Z, Fu Z, Shuai S, Babbar S, Zhao G, Li C, Machen TE.  Pseudomonas aeruginosa homoserine lactone triggers apoptosis and Bak/Bax-independent release of mitochondrial cytochrome C in fibroblasts.  Cell Microbiol 2014 Jun;16:1094-104. PMID: 24438098. PMCID: PMC4065231.
  2.  Schwarzer C, Fu Z, Morita T, Whitt AG, Neely AM, Li C, Machen TE.  Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-homoserine lactone.  J Biol Chem 2015 Mar 13;290:7247-58. PMID: 25627690. PMCID: PMC4358143.
  3.  Zhao G, Neely AM, Schwarzer C, Lu H, Whitt AG, Stivers NS, Burlison J A, White C, Machen TE., Li C. (2016). N-(3-oxo-acyl)homoserine lactone inhibits tumor growth through a unique mitochondrial apoptotic pathway independent of Bcl-2 proteins. Oncotarget 2016 Feb 2;7(5):5924-42. PMID: 56758417. PMCID: PMC4868731.
  4.  Neely AM, Zhao G, Schwarzer C, Stivers NS, Whitt AG, Meng S, Burlison JA, Machen TE, Li C. (2018). N-(3-oxo-acyl)-homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts. Cell Microbiol. 2018 Jan;20(1). PMID: 28876505. PMCID: PMC5729120.

Bax activator

  1. Olberding KE, Wang X, Zhu Y, Pan J, Rai S, Li C. (2010). Actinomycin D synergistically enhances the efficacy of the BH3 mimetic ABT-737 by down-regulating Mcl-1 expression. Cancer Biol Ther 2010 Nov 1;10(9):922-33. PMID: 20818182. PMCID: PMC3040859.
  2.  Zhao G, Zhu Y, Eno CO, Liu Y, DeLeeuw L, Burlison JA, Chaires JB, Trent J, Li C.  Activating the pro-apoptotic Bcl-2 protein Bax by a small molecule induces tumor cell apoptosis.  Mol Cell Biol 2014 Apr;34(7):1198-207. PMID: 24421393. PMCID: PMC3993561.

Ca2+ signaling and apoptosis

  1. Li C, Wang X, Vais H, Thompson CB, Foskett JK, White C.. Apoptosis regulation by Bcl-xL modulation of mammalian inositol 1,4,5-trisphosphate receptor channel isoform gating.  Proc Natl Acad Sci USA 2007 Jul 24;104:12565-70. PMID: 17636122. PMCID: PMC1941509.
  2. Eno CO, Eckenrode EF, Olberding KE, Zhao G, White C, Li C.  Distinct roles of mitochondria- and ER-localized Bcl-XL in apoptosis resistance and Ca2+ homeostasis.  Mol Biol Cell 2012 Jul;23(13):2605-18. PMID: 22573883. PMCID: PMC3386223.
  3. Huang H, Hu X, Eno CO, Zhao G, Li C, White C. (2013). An interaction between Bcl-xL and VDAC promotes mitochondrial Ca2+ uptake.  J Biol Chem 2013 Jul 5;288:19870-81.  PMID: 23720737. PMCID: PMC3707689.
  4. Huang H, Shah K, Bradbury N, Li C, White C.  Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation.  Cell Death & Disease 2014 Oct 24;5:e1482. PMID: 25341036. PMCID: PMC4237246.

ER stress-induced apoptosis 

  1. Wang X, Olberding KE, White C, Li C.  Bcl-2 proteins regulate ER membrane permeability to luminal proteins during ER stress-induced apoptosis.  Cell Death Diff  2011 Jan;18:38-47. PMID: 20539308. PMCID: PMC2947581.
  2. Wang X, Eno CO, Altman BJ, Zhu Y, Zhao G, Olberding KE, Rathmell JC, Li C.  ER stress modulates cellular metabolism.  Biochem J 2011 Apr 1;435:285-96. PMID: 21241252. PMCID: PMC3072169.
  3. Zhao G, Lu H, Li C.  Proapoptotic activities of protein disulfide isomerase (PDI) and PDIA3 protein, a role of the Bcl-2 protein Bak.  J Biol Chem 2015 Apr 3;290:8949-63. PMID: 25697536. PMCID: PMC4423685.

PubMed Information