Weei-Chin Lin, M.D., Ph.D.

Dan L. Duncan Endowed Professor

Email

weeichil@bcm.edu

Positions

Dan L. Duncan Endowed Professor: Medicine-Hematology & Oncology
Baylor College of Medicine
Houston, TX, US

Professor: Department of Molecular and Cellular Biology
Baylor College of Medicine
Houston, Texas, United States

Dan L Duncan Endowed Professor: Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas, United States

Co-Director: Cancer & Cell Biology Graduate Program
Baylor College of Medicine

Faculty: Development, Disease Models & Therapeutics Graduate Program
Baylor College of Medicine

Addresses

Alkek Building for Biomedical Research (Office): Room: ABBR-R410
Houston, TX, 77030
United States

Education

PhD from Johns Hopkins University School Of Medicine: 05/1993 - Baltimore, Maryland, United States

MD from National Taiwan University: 06/1986 - Taipei, Taiwan, Taiwan

Post-Doctoral Fellowship at Johns Hopkins University School of Medicine: 06/1994 - Baltimore, Maryland, United States

Residency at Duke University Medical Center: 06/1996 - Durham, North Carolina, United States

Clinical Fellowship at Duke University Medical Center: 06/1999 - Durham, North Carolina, United States

Certifications

Texas Medical Board

Diplomate, American Board of Internal Medicine

Subspecialty in Medical Oncology, ABIM

Subspecialty in Hematology, ABIM

Honors & Awards

Dan Duncan Professorship of Oncology: Baylor College of Medicine (01/2010)

The Leukemia & Lymphoma Society Scholar: (07/2006 - 06/2011)

General Motors Cancer Research Scholar: (01/2002 - 01/2005)

Howard Hughes Medical Institute Junior Faculty Development Award: (06/2001 - 06/2004)

Damon Runyon-Walter Winchell Physician Scientist Award: Duke University (04/1999 - 05/2001)

The Martin and Carol Macht Research Prize: Johns Hopkins University (05/1993)

Professional Interests

Cell cycle regulation
Development of cancer therapeutics
Clinical hematology

Professional Statement

I am a physician-scientist and maintain an active research program and clinical practice. My research focuses on defining mechanisms linking cell-cycle control, genome integrity, and cancer. My early studies established the cell-cycle regulation of RAG2 and V(D)J recombination, revealing a fundamental mechanism that coordinates cell-cycle progression with programmed DNA rearrangement and laying the foundation for subsequent insights into aberrant recombination and lymphomagenesis. My subsequent research has elucidated critical mechanisms of cell-cycle and DNA-damage regulation, including the roles of TopBP1, E2F1, mutant p53, and RNF144A in cancer. These discoveries have revealed key vulnerabilities underlying tumor development and therapeutic resistance. More recently, we have developed first-in-class inhibitors targeting the BRCT7/8 domains of TopBP1, translating our original discoveries in cancer biology into novel therapeutic strategies for therapy-resistant cancers.

Websites

VIICTR profile

news in research (new TopBP1 inhibitor overcomes drug resistance)

news in research (mutant p53 and immunotherapy)

news in research (TopBP1 inhibitor and MYC)

news in research (DNA2 inhibitors)

news in research (ER loss in breast cancer)

news in research (cisplatin resistance in lung cancer and ovarian cancer)

news in research (target TopBP1 in cancer)

Medicine/Hematology Oncology

Cancer & Cell Biology Graduate Program

Development, Disease Models & Therapeutics Graduate Program

Rivkin Center: Novel Approaches to Target MYC in Ovarian Cancer.

Selected Publications

List of Published Work in My Bibliography " ;
Fang-Tsyr Lin, Shwu-Jiuan Lin, Kang Liu , Yang Xiao, Lidija A Wilhelms Garan, Helena Folly-Kossi, Weei-Chin Lin. " Development of a structurally distinct TopBP1 inhibitor that enhances PARP blockade and reverses osimertinib resistance " Sci Adv.. 2026 Aug 7; 7 (12(32)) : eaeg1996.
Pubmed PMID: 42555732.
Kang Liu, Lidija AW Garan, Fang-Tsyr Lin, Weei-Chin Lin. " Mutant p53 variants differentially impact replication initiation and activate cGAS-STING to affect immune checkpoint inhibition " Communications Biology. 2025 ; 8(1) (1522)
Pubmed PMID: 41193733.
Fang-Tsyr Lin, Kang Liu, Lidija A Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, Shwu-Jiuan Lin, Weei-Chin Lin. " A small-molecule inhibitor of TopBP1 exerts anti-MYC activity and synergy with PARP inhibitors " Proc Natl Acad Sci U S A. 2023 Oct 25;
Pubmed PMID: 37878724.
Folly-Kossi H, Graves JD, Wilhelms Garan LA, Lin FT, Lin WC.. " DNA2 nuclease inhibition confers synthetic lethality in cancers with mutant p53 and synergizes with PARP inhibitors. " Cancer Res Commun.. 2023 Oct 16; 3 (10) : 2096-112.
Pubmed PMID: 37756561.
Lin WC, Lin FT. " Super-enhanced MARCO variant drives triple-negative breast cancer progression " Proc Natl Acad Sci U S A.. 2022 Dec 5; 119 (50) : e2217953119.
Pubmed PMID: 36469785.
Garan LA, Xiao Y, Lin WC. " 14-3-3tau drives estrogen receptor loss via ERalpha36 induction and GATA3 inhibition in breast cancer. " Proc Natl Acad Sci U S A.. 2022 Oct 17; 119 (43) : e2209211119.
Pubmed PMID: 36252018.
Ho SR, Lee YC, Ittmann MM, Lin FT, Chan KS, Lin WC. " RNF144A deficiency promotes PD-L1 protein stabilization and carcinogen-induced bladder tumorigenesis " Cancer Lett.. 2021 Aug 13; 520 (2021) : 344-360.
Pubmed PMID: 34400221.
Liu K, Graves JD, Lin FT, Lin WC. " Overexpression of TopBP1, a canonical ATR/Chk1 activator, paradoxically hinders ATR/Chk1 activation in cancer " J Biol Chem. 2021 Feb 5; https://doi.org/10.1016/j.jbc.2021.100382
Pubmed PMID: 33556369.
Xiao Y, Lin FT, Lin WC. " ACTL6A promotes repair of cisplatin-induced DNA damage, a new mechanism of platinum resistance in cancer " Proc Natl Acad Sci U S A. 2021 Jan 19; 118 (3) : 1-12.
Pubmed PMID: 33408251.
Graves JD, Lee YJ, Liu K, Li G, Lin FT, Lin WC. " E2F1 sumoylation as a protective cellular mechanism in oxidative stress response " Proc Natl Acad Sci U S A. 2020 Jun 30; 117 (26) : 11958-14969.
Pubmed PMID: 32541040.
Liu K, Graves JD, Lee YJ, Lin FT, Lin WC. " Cell Cycle-Dependent Switch of TopBP1 Functions by Cdk2 and Akt " Mol Cell Biol. 2020 Mar 30; 40 (8) : 1-19.
Pubmed PMID: 31964753.
Lee YJ, Ho SR, Graves JD, Xiao Y, Huang S, Lin WC. " CGRRF1, a growth suppressor, regulates EGFR ubiquitination in breast cancer " Breast Cancer Res. 2019 Dec 4; 21 (1) : 1-22.
Pubmed PMID: 31801577.
Ho SR, Lin WC. " RNF144A sustains EGFR signaling to promote EGF-dependent cell proliferation " J Biol Chem. 2018 Oct 19; 293 (42) : 16307-16323.
Pubmed PMID: 30171075.
Liu K, Lin FT, Graves JD, Lee YJ, and Lin WC.. " Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin " Proc Natl Acad Sci U S A. 2017 Apr 24; doi: 10.1073/pnas.1619832114 (PNAS Early Edition) : 1-10.
Pubmed PMID: 28439015.
Mahanic CS, Budhavarapu V, Graves JD, Li G, Lin WC.. " Regulation of E2 promoter binding factor 1 (E2F1) transcriptional activity through a deubiquitinating enzyme, UCH37. " J Biol Chem. 2015 Oct 30; 290 (44) : 26508-22.
Pubmed PMID: 26396186.
Ho SR, Lee YJ, Lin WC.. " Regulation of RNF144A E3 Ubiquitin Ligase Activity by Self-association through Its Transmembrane Domain. " J Biol Chem. 2015 Sep 18; 290 (38) : 23026-38.
Pubmed PMID: 26216882.
Chowdhury P, Lin GE, Liu K, Song Y, Lin FT, Lin WC. " Targeting TopBP1 at a convergent point of multiple oncogenic pathways for cancer therapy. " Nat Commun.. 2014 Nov 17; (5) : 5476.
Pubmed PMID: 25400145.
Ho SR, Mahanic CS, Lee YJ, Lin WC. " RNF144A, an E3 ubiquitin ligase for DNA-PKcs, promotes apoptosis during DNA damage. " Proc Natl Acad Sci U S A.. 2014 Jul 1; 111 (26) : E2646-55.
Pubmed PMID: 24979766.
Xiao Y, Lin VY, Ke S, Lin GE, Lin FT, Lin WC. " 14-3-3τ promotes breast cancer invasion and metastasis by inhibiting RhoGDIα. " Mol Cell Biol.. 2014 May 12; 34 (14) : 2635-49.
Pubmed PMID: 24820414.
Liu K, Graves JD, Scott JD, Li R, Lin WC. " Akt Switches TopBP1 Function from Checkpoint Activation to Transcriptional Regulation through Phosphoserine Binding-Mediated Oligomerization. " Mol Cell Biol.. 2013 Dec ; 33 (23) : 4685-700.
Pubmed PMID: 24081328.
Budhavarapu VN, White ED, Mahanic CS, Chen L, Lin FT, Lin WC. " Regulation of E2F1 by APC/C (Cdh1) via K11 linkage-specific ubiquitin chain formation. " Cell Cycle. 2012 May 15; 11 (10) : 2030-8.
Pubmed PMID: 22580462.
Liu K, Ling S, Lin WC. " TopBP1 mediates mutant p53 gain of function through NF-Y and p63/p73. " Mol. Cell. Biol.. 2011 Nov ; 31 (22) : 4464-81.
Pubmed PMID: 21930790.
Ling S, Lin WC. " EDD Inhibits ATM-mediated Phosphorylation of p53. " J. Biol. Chem.. 2011 Apr 29; 286 (17) : 14972-82.
Pubmed PMID: 21383020.
Wang B, Liu K, Lin HY, Bellam N, Ling S, Lin WC. " 14-3-3{tau} Regulates Ubiquitin-Independent Proteasomal Degradation of p21, a Novel Mechanism of p21 Downregulation in Breast Cancer. " Mol. Cell. Biol.. 2010 Mar ; 30 (6) : 1508-27.
Pubmed PMID: 20086099.
Paik JC, Wang B, Liu K, Lue JK, Lin WC. " Regulation of E2F1-induced Apoptosis by the Nucleolar Protein RRP1B. " J. Biol. Chem.. 2010 Feb 26; 285 (9) : 6348-63.
Pubmed PMID: 20040599.
Liu K, Bellam N, Lin HY, Wang B, Stockard CR, Grizzle WE, Lin WC. " Regulation of p53 by TopBP1: a potential mechanism for p53 inactivation in cancer. " Mol. Cell. Biol.. 2009 May ; 29 (10) : 2673-93.
Pubmed PMID: 19289498.
Yang SZ, Lin FT, Lin WC. " MCPH1/BRIT1 cooperates with E2F1 in the activation of checkpoint, DNA repair and apoptosis. " EMBO Rep.. 2008 Sep ; 9 (9) : 907-15.
Pubmed PMID: 18660752.
Liu K, Paik JC, Wang B, Lin FT, Lin WC. " Regulation of TopBP1 oligomerization by Akt/PKB for cell survival. " EMBO J.. 2006 Oct 18; 25 (20) : 4795-807.
Pubmed PMID: 17006541.
Luo Y, Lin FT, Lin WC. " ATM-mediated stabilization of hMutL DNA mismatch repair proteins augments p53 activation during DNA damage. " Mol. Cell. Biol.. 2004 Jul ; 24 (14) : 6430-44.
Pubmed PMID: 15226443.
Liu K, Luo Y, Lin FT, Lin WC. " TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-independent and E2F1-specific control for cell survival. " Genes Dev.. 2004 Mar 15; 18 (6) : 673-86.
Pubmed PMID: 15075294.
Liu K, Lin FT, Ruppert JM, Lin WC. " Regulation of E2F1 by BRCT domain-containing protein TopBP1. " Mol. Cell. Biol.. 2003 May ; 23 (9) : 3287-304.
Pubmed PMID: 12697828.
Lin WC, Lin FT, Nevins JR. " Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation " Genes Dev. 2001 Jul 15; 15 (14) : 1833-44.
Pubmed PMID: 11459832.
Lin WC, Desiderio S. " V(D)J recombination and the cell cycle " Immunol Today .. 1995 Jun 16; 16 (6) : 279-89.
Pubmed PMID: 7662097.
Lin WC, Desiderio S. " Cell cycle regulation of V(D)J recombination-activating protein RAG-2 " Proc Natl Acad Sci U S A. 1994 Mar 29; 91 (7) : 2733-7.
Pubmed PMID: 8146183.
Lin WC, Desiderio S. " Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation " Science. 1993 May 14; 260 (5110) : 953-9.
Pubmed PMID: 8493533.

Intellectual Property

Method of Treating Cancer That Overexpresses TopBP1: Method Patent #US 9,636,323 (Approved); Establishes TopBP1 as a therapeutic target and provides treatment strategies for TopBP1-overexpressing cancers.; Co Inventors: Weei-Chin Lin, Pinki Chowdhury, Gregory E. Lin, Kang Liu, Yongcheng Song, Fang-Tsyr Lin

Novel Small Molecule Inhibitors of TopBP1-BRCT7/8 That Exert anti-MYC Activity and Synergy with Inhibitors of PARP1/2 and PARP14: Product Patent #PCT/US24/48843 (Pending); Novel compounds that suppress MYC signaling and enhance the activity of PARP-targeted therapies.; Co Inventors: Weei-Chin Lin, Fang-Tsyr Lin

TopBP1-BRCT7/8 Inhibitors and Methods of Use: Product Patent #64/125,660 (Pending); Novel TopBP1-BRCT7/8 inhibitors and their therapeutic applications in cancer treatment.; Co Inventors: Weei-Chin Lin, Fang-Tsyr Lin