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:

Associate Professor, Department of Medicine, University of Louisville School of Medicine
Member, Experimental Therapeutics & Diagnostics Program, 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 South 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:

A cancer vaccine based on exosomes of stem cells 

  1. Meng S, Whitt AG, Tu A, Eaton JW, Li C, Yaddanapudi K.  Isolation of exosome-enriched extracellular vesicles carrying granulocyte-macrophage colony-stimulating factor from embryonic stem cells.  Journal of Visualized Experiments 2021 Nov 11;177.  doi: 10.3791/60170.  PMID: 34842232.
  2. Donninger H, Li C, Eaton JW, Yaddanapudi K.  Cancer vaccines: promising therapeutics or an unattainable dream.  Vaccines (Basel) 2021 Jun 18;9(6):668.  doi: 10.3990/vaccines9060668.  PMID: 34207062.  PMCID: PMC8233841.
  3. Li C, Donninger H, Eaton JW, Yaddanapudi K.  Regulatory role of immune cell-derived extracellular vesicles in cancer: the message is in the envelope.  Frontiers in Immunology 2020 Jul 16;11:1525.  PMID: 32765528.  PMCID: PMC7378739.
  4. Yaddanapudi K, Meng S, Whitt AG, Al Rayyan N, Richie J, Tu A, Eaton JW, Li C.  Exosomes from GM-CSF expressing embryonic stem cells are an effective prophylactic vaccine for cancer prevention. OncoImmunology 2019 Jan 9;8(3):1561119.  doi:  10.1080/2162402X.2018.1561119.  eCollection 2019.  PMID: 30723593.  PMCID: PMC6350682.
  5. Yaddanapudi K, Li C, Eaton JW.  Vaccination with induced pluripotent stem cells confers protection against cancer. Stem Cell Investigation 2018 Jul 23;5:23.  doi: 10.21037/sci.2018.07.03.  eCollections 2018.  PMID: 30148156.  PMCID: PMC6087803.

Anti-tumor activity of a homoserine lactone

  1. Neely AM, Zhao G, Schwarzer C, Stivers NS, Whitt AG, Meng S, Burlison JA, Machen TE, Li C.  N-(3-oxo-acyl)-homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts.  Cell Microbiology 2018 Jan;20(1):10.1111/cmi.12787.  Epub 2017 Oct 9.  PMID: 28876505.  PMCID: PMC5729120.
  2. Zhao G, Neely AM, Schwarzer C, Lu H, Whitt AG, Stivers NS, Burlison JA, White C, Machen TE, Li C.  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.  doi: 10.18632/oncotarget.6827.  PMID: 56758417.  PMCID: PMC4868731.
  3. 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.  Journal of Biological Chemistry 2015 Mar 13;290(11):7247-58.  doi: 10.1074/jbc.M114.620039.  Epub 2015 Jan 27.  PMID: 25627690.  PMCID: PMC4358143.
  4. Schwarzer C, 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 Microbiology 2014 Jul;16(7):1094-104.  doi: 10.111/cmi.12263.  Epub 2014 Feb 13.  PMID: 24438098.  PMCID: PMC4065231.

Bax activator

  1. Zhao G, Zhu Y, Eno CO, Liu Y, DeLeeuw L, Burlison JA, Chaires JB, Trent J, Li C.  Activation of the pro-apoptotic Bcl-2 protein Bax by a small molecule induces tumor cell apoptosis.  Molecular & Cellular Biology 2014 Apr;34(7):1198-207.  doi: 10.1128/MCB.00996-13.  Epub 2014 Jan 13.  PMID: 24421393.  PMCID: PMC3993561.
  2. Olberding KE, Wang X, Zhu Y, Pan J, Rai S, Li C.  Actinomycin D synergistically enhances the efficacy of the BH3 mimetic ABT-737 by down-regulating Mcl-1 expression.  Cancer Biology & Therapeutics 2010 Nov 1;10(9):918-22.  doi: 10.4161/cbt.10.9.13274.  Epub 2010 Nov 1.  PMID: 20818182.  PMCID: PMC3040859.
  3. Brock SE, Li C, Wattenberg BW.  The Bax carboxyl-terminal hydrophobic helix does not determine organelle-specific targeting but is essential for maintaining Bax in an inactive state and for stable mitochondrial membrane insertion.  Apoptosis 2010 Jan;15:14-27.  doi: 10.1007/s10495-009-0410-2.  PMID:19809877.

Ca2+ signaling and apoptosis

  1. 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 23;5(10):e1482.  doi: 10.1038/cddis.2014.419.  PMID: 25341036.  PMCID: PMC4237246.
  2. Huang H, Hu X, Eno CO, Zhao G, Li C, White C.  An interaction between Bcl-xL and VDAC promotes mitochondrial Ca2+ uptake.  Journal of Biological Chemistry 2013 Jul 5;288(27):19870-81.  doi: 10.1074/jbc.M112.448290.  Epub 2013 May 17.  PMID: 23720737.  PMCID: PMC3707689.
  3. 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.  Molecular Biology of the Cell 2012 Jul;23(13):2605-18.  doi: 10.1091/mbc.E12-02-0090.  Epub 2012 May 9.  PMID: 22573883.  PMCID: PMC3386223.
  4. 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.  Proceedings of the National Academy of Science USA 2007 Jul 24;104(30):12565-70.  doi: 10.1073/pnas.0702489104.  Epub 2007 July16.  PMID: 17636122.  PMCID: PMC1941509.

ER stress-induced apoptosis 

  1. Zhao G, Lu H, Li C.  Proapoptotic activities of protein disulfide isomerase (PDI) and PDIA3 protein, a role of the Bcl-2 protein Bak.  Journal of Biological Chemistry 2015 Apr 3;290(14):8949-63.  doi: 10.1074/jbc.M114.619353.  Epub 2015 Feb 19.  PMID: 25697536.  PMCID: PMC4423685.
  2. Wang X, Eno CO, Altman BJ, Zhu Y, Zhao G, Olberding KE, Rathmell JC, Li C.  ER stress modulates cellular metabolism.  Biochemical Journal 2011 Apr 1;435(1):285-96.  doi: 10.1042/BJ20101864.  PMID: 21241252.  PMCID: PMC3072169.
  3. 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 & Differentiation 2011 Jan;18(1):38-47.  doi: 10.1038/cdd.2010.68.  Epub 2010 Jun 11.  PMID: 20539308.  PMCID: PMC2947581.

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