Academic Title:
Professor
Primary Appointment:
Biochemistry and Molecular Biology
Additional Title:
Professor
Email:
Location:
Biochemistry and Molecular Biology 329
Phone (Primary):
410-706-7469
Education and Training
- Ph.D., Genetics and Molecular Biology, University of Delaware, Thesis Advisor - Dr. Daniel T. Simmons
- Post-doctoral research fellow, Department of Molecular Biology, Princeton University, Mentor - Dr. Arnold J. Levine
Biosketch
- 1997-1998 - Faculty member at the Department of Dermatology, University of Michigan Medical Center, Ann Arbor, MI.
- 1998-2004 - Assistant Professor (Tenure Track) at the Division of Gynecologic Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
- 1998-2004 - Member, University of Michigan Comprehensive Cancer Center and Member, Connective Tissue Oncology at the University of Michigan. Comprehensive Cancer Center.
- 2000-2004 - Graduate faculty member in Program in Biomedical Sciences, Cellular and Molecular Biology Graduate Program and Cancer Biology Training Program at the University of Michigan.
- 2005-2015 - Associate Professor with Tenure, Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH.
- 2005-2016 - Full Member, The Ohio State University Comprehensive Cancer Center, Graduate Faculty, Integrated Biomedical Science, Graduate Program, Molecular, Cellular & Developmental Biology Graduate Program, and Ohio State Biochemistry Graduate Program, The Ohio State University.
- 2016 - Professor with tenure, Department of Pediatrics, College of Medicine, The Ohio State University.
- 2016-Present - Professor with tenure, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland in Baltimore.
- 2016-Present – Full member, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center.
- 2016-Present - Graduate Faculty, Cancer Biology Track, Molecular Medicine Graduate Program, School of Medicine, University of Maryland, Baltimore, MD.
Research/Clinical Keywords
IL-6, GP130, STAT3, PARP, CDK4/6
Highlighted Publications
- Lin L., Hutzen B, Ball S., Zuo M., Deangelis S., Foust E., Pandit B, Ihnat MA, Shenoy S., Kulp S., Li P-K., Li C., Fuchs J., and Lin J. Novel STAT3 phosphorylation inhibitors exhibit potent growth suppressive activity in breast and pancreatic cancer cells. Cancer Research 70:2445-2454 (2010).
- Liu Y., Li P-K., Li C., and Lin J. Inhibition of IL-6/STAT3 Signaling in Human Liver Cancer Cells Blocks the Anti-Apoptotic Activity of IL-6. J. Biol. Chem. 285:27429-27439 (2010).
- Liu, Y., Liu, A., Li, H., Li, C., and Lin, J.Celecoxib Inhibits Constitutive and Interleukin 6-Induced STAT3 Phosphorylation in Human Hepatocellular Carcinoma Cell. Cancer Prevention Research 4: 1296-1305 (2011).
- Lin L., Liu A., Peng Z., Lin H., Li C., Li P-K., and Lin J.STAT3 is necessary for proliferation and survival in colon cancer-initiating cells. Cancer Research 71:7226-7237 (2011)
- Lin L., Hutzen B, Lee, H-F, Peng Z., Lin H., Sun, D., Li P-K., Li C., Korkaya, H., Wicha M., and Lin J. Evaluation of STAT3 Signaling in ALDH+ and ALDH+/CD44+/CD24- Subpopulations of Breast Cancer Cells. PloS ONE 8(12):e82821 (2013).
Additional Publication Citations
- Li H., Liu A., Zhao Z., Xu Y., Lin J., Jou D., and Li, C. Fragment-based Drug Design and Drug Repositioning Using Multiple Ligand Simultaneous Docking (MLSD): Identifying Celecoxib and Template Compounds as Novel Inhibitors of STAT3. J. Medicinal Chemistry 54: 5592-5596 (2011).
- Lin, L., Benson, D.M. Jr., DeAngelis, S., Bakan, C. E., Li, P-K., Li, C., and Lin, J. A small molecule, LLL12 inhibits constitutive STAT3 and IL-6-induced STAT3 signaling and exhibits potent growth suppressive activity in human multiple myeloma cells. International Journal of Cancer 130:1459-1469 (2012).
- Liu, A., Liu, Y., Lin, L., Jin, Z., Yang, J., Hu, Q., Xu, Z., Wang, H., Li, C.,Lin, J. XZH-5 inhibits STAT3 phosphorylation and enhances the cytotoxicity of chemotherapeutic drugs in human breast and pancreatic cancer cells. PloS ONE 7(10):e46624 (2012).
- Yu W., Xiao H., Lin J., Li C. Discovery of Novel STAT3 Small Molecule Inhibitors via In Silico Site-Directed Fragment-Based Drug Design. J. Medicinal Chemistry 56:4402-4412 (2013).
- Li H., Kumari V., Lin L., Jou D., Lin J., Li C. Drug Design Targeting Protein-Protein Interactions (PPIs) Using Multiple Ligand Simultaneous Docking (MLSD) and Drug Repositioning: Discovery of Raloxifene and Bazedoxifene as Novel Inhibitors of IL-6/GP130 Interface. J. Medicinal Chemistry 57:632-641 (2014).
- Zhao C., Xiao H., Wu X., Li, C., Lin, J. Rational Combination of MEK inhibitor and STAT3pathway modulator for K-RAS mutant pancreatic and colon cancer cells. Oncotarget. 6:14472-87 (2015).
- Zhao C, Li H, Lin HJ, Yang S, Lin J, Liang G. Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism. Trends Pharmacol Sci. 37(1):47-61 (2016)
- Wu X., Tang W., Marquez R., Li K., Highfill C., He F., Lian J., Lin J., Fuchs J., Ji M., Li L., Xu L. Overcoming radiation resistance of pancreatic cancer by inhibiting STAT3 signaling. Oncotarget 7(10):11708-11723 (2016).
-
Sirkisoon S, Carpenter R, Rimkus T, Doheny D, Zhu D, Aguayo N, Xing F, Chan M, Ruiz J, Metheny Barlow L, Strowd R, Lin J, Regua A, Arrigo A, Anguelov M, Pasche B, Debinski W, Watabe K, and Lo H-W. TGLI1 transcription factor mediates breast cancer brain metastasis via activating metastasis-initiating cancer stem cells and astrocytes in the tumor microenvironment. Oncogene 39: 64-78, (2020).
-
Zhao C, Yang L, Zhou F, Yu Y, Du X, Xiang Y, Li C, Huang X, Xie C, Liu Z, Lin J, Wang L, Liang G, and Cui R. Feedback activation of EGFR is the main cause for STAT3 inhibition-irresponsiveness in pancreatic cancer cells. Oncogene 39:3997-4013, (2020).
-
Regua AT, Aguayo NR, Jalboush SA, Doheny DL, Manore SG, Zhu D, Wong GL, Arrigo A, Wagner CJ, Yu Y, Thomas A, Chan MD, Ruiz J, Jin G, Strowd R, Sun P, Lin J, Lo HW. TrkA Interacts with and Phosphorylates STAT3 to Enhance Gene Transcription and Promote Breast Cancer Stem Cells in Triple-Negative and HER2-Enriched Breast Cancers. Cancers (Basel). 13(10):2340, (2021).
-
Lin H., Liu Y., Lofland D., Lin J. Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity. Cancers (Basel). 14(2):285, (2022).
- Lin H., Liu Y., Caroland K., Lin J. Polarization of Cancer-Associated Macrophages Maneuver Neoplastic Attributes of Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 15(13):3507, (2023).
Research Interests
The research interests of my laboratory are focused on the roles of inflammatory Interleukin (IL)-6 cytokine plays in cancer. The IL-6 family of cytokines, in particular IL-6, is considered as one of the most important cytokine families during tumorigenesis and metastasis. IL-6 binds to its receptor then recruits Glycoprotein 130 (GP130) to form the heterotrimer and triggers a signaling cascade downstream including Signal Transducer and Activator of Transcription 3 (STAT3) and AKT pathways. Serum IL-6 levels in cancer patients are correlated with poor prognosis, advanced stage, and/or metastasis.
In addition, IL-6 signaling is involved in promoting proliferation, survival, Inflammation, invasion, and metastasis of cancer cells. One of the major downstream effectors of IL-6 is STAT3. Persistent activation of STAT3 is frequently detected in many types of human cancers. We are studying the mechanisms of IL-6 signaling in promoting cancer progression, survival, proliferation, and tumorigenesis. The laboratory is also developing novel structure-based design and drug repositioning of small molecule compounds as well as existing FDA-approved drugs that selectively target persistent IL-6/GP130 signaling in cancer cells as novel cancer therapeutic approaches. In addition, our lab is studying the crosstalk between IL-6/GP130/STAT3 signaling and PARP and CDK4/6 pathaways.
Awards and Affiliations
2010 Received an AACR top-rated abstract award at the AACR Annual Meeting in Washington D. C.
2015 Feature Editorial Academy (Editorial Board) in May issue of the International Journal of Oncology.
Grants and Contracts
1. NIH/NCI R21 (PI-Lin)
2. VA Merit award (PI-Lin)
3. DOD BCRP award (PI-Lin)
Community Service
International Service
2012-2015 Review of research grant of the Health and Health Services Research Fund of the Food and Health Bureau, Hong Kong SAR Government.
2012-present International Journal of Biochemistry and Molecular Biology (ISSN: 2152-4114): Senior Editorial Board.
2013 Review of a cancer research grant for the National Medical Research Council Ministry of Health, Singapore.
2014-Present International Journal of Oncology: Editorial Academy (Editorial Board).
2014-2016 BMC Cancer: Editorial Board.
National Service
2005 WISC grants reviewer, American Association for the Advancement of Science, Washington DC.
2005-2010 The Congressionally Directed Medical Research Programs (CDMRP) Breast Cancer Research Program, Review Committee (Clinical and Experimental Therapeutics # 2 and # 4, and TRN1 panels).
2005-2008 External Consulting and Advisory Team Member, Global Clinical Development for anti-cancer drugs, Global Health Sector, SRA, International, Inc., Fairfax, VA
2009-2010 NIH Special Emphasis Panel/Scientific Review Group 2009/10 ZRG1 OTC-K.
2013 National Cancer Institute Special Emphasis Panel; ZCA1 SRLB-J (O1) S.
2013-2015 Pancreatic Cancer Action Network-AACR Research Grants Scientific Review Committee.
2013-present American Journal of Cancer Research (ISSN: 2156-6976): Senior Editorial Board.
2015-2016 Pennsylvania Department of Health: Serve as a final performance external reviewer of a funded cancer research grant.
2016 National Cancer Institute Special Emphasis Panel (SEP #5) for NCI Omnibus R21 and NCI Omnibus R03 grant reviews.
2017-2022 Cancer Drug Development & Therapeutics (CDDT) study section to review NIH applications from small business.
2021 Swiss Cancer Research foundation & Swiss Cancer League grant reviewer.
2023 National Cancer Institute Special Emphasis Panel for NCI Omnibus R21 and NCI Omnibus R03 grant reviews.
Local Service
Institutional Service
1999-2004 Search Committee for the recruitment of Gynecologic Oncology fellows, University of Michigan.
2000-2003 Medical Scientists Training program mentor, University of Michigan.
2000-2003 Research Executive Committee in the Department of OB/GYN at the University of Michigan
2000-2004 Cancer Biology Training Program mentor, University of Michigan.
2005 Library oversight Committee, Department of Pediatrics, The Ohio State University.
2009-2010 Scholarship Oversight Committee Volunteer, Department of Pediatrics, The Ohio State University.
2010 Annual Research retreat planning Committee, Department of Pediatrics, The Ohio State University.
2015-2016 Faculty Search Committee, Department of Pediatrics, The Ohio State University.
2016-present Faculty Search Committee, Departments of Biochemistry and Molecular Biology and Pathlogy, University of Maryland, School of Medicine.
Scientific judges for poster presentations
2005-2013 The Ohio State University Medical Center Annual Scientific Retreat.
2006-2007 The Ohio State University Comprehensive Cancer Center Annual Scientific Retreat.
2010-2015 The Research Institute at Nationwide Children’s Hospital, Columbus OH.
2013 IGP Symposium, The Ohio State University graduate Programs.
2013 OSBP graduate students recruitment and interviews.
2014 Denman Undergraduate Research Forum, The Ohio State University.
Graduate Student-Doctoral Committees, University of Michigan
Graduate Student-Doctoral Committees, The Ohio State University
Graduate Students-Thesis Advisor (Dr. Lin as the thesis advisor):
2004 Ling Cen, Ph.D student, Ohio State Biochemistry Program, Ohio State University (Graduated in 2007): working at the Mayo Clinics, MN as a staff member.
2006 Jacquie Lieblein, M.S. student, Ohio State Biochemistry Program, The Ohio State University (Graduated in 2008): became a Ph.D. student at the Ohio State Univ.
2006 Matthew Sobo, M.S. student, MCDB, The Ohio State University (Graduated in 2010).
2008 Sarah Ball, Ph.D student, MCDB, The Ohio State University (Graduated in 2011): teaching position at The Ohio State University.
International graduate Students-Ph.D. Thesis (Dr. Lin as the thesis co-advisor):
2012-2015 Chengguang Zhao, Ph.D. student, Nanjing University of Science and Technology, China.
2015-2016 Jilai Tian Ph.D. student, Southeast University, China.
Medical doctor Fellows- Lin Laboratory, University of Michigan (Dr. Lin as the mentor):
1999-2000 Melinda Huang, M.D. (Currently is a faculty member/physician in another University/hospital)
2000-2001 William Burke, M.D. (Currently is a faculty member/physician in another University/hospital)
2001-2002 Thomas Reid, M.D. (Currently is a faculty member/physician in another University/hospital)
Medical doctor Fellows- Lin Laboratory, The Ohio State University (Dr. Lin as the thesis mentor):
2005-2007 Beng Huh, M.D. (Currently is a faculty member/physician in another University/hospital)
2006-2008 Jason Canner, M.D. (Currently is a faculty member/physician in another University/hospital)
2009-2010 Grace Ominoe, M.D. (Currently is a physician in another hospital)
2010-2011 Susan Reed, M.D. (Currently is a faculty member/physician at the Ohio State University/Nationwide Children’s Hospital)
2002-2003 Dana Gossett, M.D. (Currently is a faculty member/physician in another University/hospital)
Professional Activity
1998-present Full member, American Association for Cancer Research (AACR).
Major Invited Speeches
International
2002 Lin J. “A novel AKT inhibitor targets endometrial cancer cells with PTEN mutation”, International Symposium on Cell and Molecular Biology of Endometrial Carcinoma, Kitasato Institute & University, Tokyo, Japan.
2002 Lin J. “Target endometrial and ovarian cancer cells with a novel AKT inhibitor”, National Yang-Ming University, College of Medicine, Taipei, Taiwan.
2012 Lin J. “IL-6/STAT3 signaling in cancer”. The German Cancer Research Center, Heidelberg, Germany