Tao Lu, PhD
Assistant Professor of Pharmacology & Toxicology
I have an extensive background in signaling transduction, molecular and cellular biology, biochemistry, genetics, and pharmacology with specific expertise in NF-kB signaling, post-translational modification, cancer epigenetics, and drug discovery. Born in a physician and medical professor’s family, I was fascinated by medical science from a very young age. I studied signaling transduction in cell death during my graduate study with Dr. Ronald L. Mellgren. My postdoctoral training was with the world renowned cancer biologist and geneticist Dr. George R. Stark, who famously contributed to the development of both Western Blot and Northern Blot techniques that are widely used by the scientists all over the world. Dr. Stark also discovered interferon/JAK/Stat pathway. I was an Assistant Professor at Lerner College of Medicine at Case Western Reserve University (CWRU) before I relocated to Indianapolis.
Assistant Professor (tenure track), Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN
Adjunct Assistant Professor, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
Adjunct Assistant Professor, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
Assistant Professor in Molecular Medicine, Lerner College of Medicine at Case Western Reserve University (CWRU), Cleveland, OH
Project Scientist, Department of Molecular Genetics, Cleveland Clinic, Cleveland, OH
Research Associate, Department of Molecular Genetics, Cleveland Clinic, Cleveland, OH
Keynote Speaker, "Cancer-2018", International Conference on Cancer Research
Faculty Member of the Year, Indiana University School of Medicine, Indianapolis, IN
Trustees’ Teaching Award, Indiana University School of Medicine, Indianapolis, IN
Honorary Keynote Speaker, The Larry Gentry Research Forum, University of Toledo School of Medicine, Toledo, OH
Elwert Award in Medicine, Indiana University School of Medicine, Indianapolis, IN
GlaxoSmithKline's Discovery Fast Track Challenge Nominee, Indiana University, Indianapolis, IN
National Pew Scholar Nominee in Cancer Research, Indiana University, Indianapolis, IN
Young Investigator Travel Award, International Cytokine and Interferon Society Conference
Fellow, Leadership in Academic Medicine Program (LAMP), Indiana University, Indianapolis, IN
F1000 Prime for High Impact Publication, twice
Walther Scholar, Indiana University Walther Oncology Center, Indianapolis, IN
ICS Young Investigator Award, Tri-Society [Society of Leukocyte Biology (SLB) & ICS & ISICR] Conference
Seymour and Vivian Milstein Young Investigator Award, International Society of Interferon & Cytokine Research (ISICR) & ICS Conference
Innovator Award, Cleveland Clinic, Cleveland, OH
Young Investigator Travel Award, International Cytokine Society (ICS) Conference
Young Investigator Travel Award, International Society of Interferon & Cytokine Research (ISICR) Conference
Innovator Award, Cleveland Clinic, Cleveland, OH
Liberato J.A. DiDio Graduate Research Award, University of Toledo School of Medicine, Toledo, OH
International Professional Activities
(selected from over 20 journals): Molecular Cellular Biology (MCB), Proc Natl Acad Sci (PNAS), Oncogene, Cancer Research, FASEB J, Scientific Report, Cancer Letter, J Virology, European Journal of Cell Biology (EJCB)
Advisory Board, International BIT Annual World Congress of Molecular and Cellular Biology
Medical Research Council (MRC), England
2nd International Summit on Integrative Biology
International Conference on Retroviruses and Novel Drugs
Austrian Science Fund (FWF), Austrian Special Research Program (SFB)
Editorial Board, Journal of Clinical Pharmacology and Toxicology (JCPT)
The Welcome Trust/DBT India Alliance, Biomedical Fellowship Program
Editorial Board, Journal of Pharmacology Research and Toxicology
Editorial Board, Clinical Cancer Drugs
Editorial Board, The Journal of Gastroenterology & Digestive Systems
Editorial Board, SM Journal of Carcinogenesis & Mutagenesis
Editorial Board, Journal of Gastroenterology, Hepatology, and Endoscopy
Editorial Board, The Scientific Pages of Drug Design and Development
International Conference for Biomarkers and Clinical Research
Lu, T and Prabhu, L. Small molecule protein arginine methyltransferase 5 (PRMT5) inhibitors and methods of treatment. International Patent Application PCT/US2017/058572, filed on October 26, 2017
Lu, T and Prabhu, L. Small molecule protein arginine methyltransferase 5 (PRMT5) inhibitors and methods of treatment. U.S. Provisional Patent Application 62/534,969, filed on July 20, 2017
Lu, T and Prabhu, L. Small molecule protein arginine methyltransferase 5 (PRMT5) inhibitors and methods of treatment. U.S. Provisional Patent Application 62/413,341, filed on October 26, 2016
Lu, T and Stark GR. Discovery of the FBXL11 as the negative regulator of NFkB. Filed to the Cleveland Clinic Invention Disclosure in July, 2007, in the process of provisional patent application.
Lu, T, Burdelya, LG, Stark GR and Gudkov AV. Methods of inhibiting apoptosis using latent TGFb. U.S. provisional Patent No. 60/526,667, filed December 2, 2004.
Selected from 50 publications, Complete list of published work can be found at:
1. Prabhu, L, Wei, H, Chen, L, Ozlem, D, Amero, A, Sandusky, G, Sun, E, Wang, J, Mo, J, Safa, A, Korc, M, Zhang, Z, and Lu, T*. Innovative AlphaLISA discovers a novel small-molecule inhibitor targeting PRMT5 in pancreatic and colon cancers. Oncotarget 8(25): 39963-39977, 2017. * Corresponding author. - 1) Selected for Cover Page, Priority Paper, 2) Honorable Mention Award, Cancer Research Day, 3) Honorable Mention, Erica M. Daniel Kepner Award for Scientific Achievement
2. Martin, M, Hua, L, Wang, B, Wei, H, Prabhu, L, Hartley, AV, Jiang, G, Liu, Y, and Lu, T*. Novel serine 176 phosphorylation of YBX1 activates NF-kB in colon cancer. J Biol Chem 292 (8): 3433-3444, 2017. * Corresponding author
3. Wang, B, Wei, H, Prabhu, L, Zhao, W, Martin, M, Hartley, A, and Lu, T*. Role of novel serine 316 phosphorylation of the p65 subunit of NF-kB in differential gene regulation. J Biol Chem 290 (33): 20336-20347, 2015 * Corresponding author - Selected for Donald Bowman Award
4. Lu, T* and Stark, GR*. NF-kB, regulation by methylation. Cancer Res 75 (18): 3692-3695, 2015. * Corresponding authors
5. Wei, H, Wang, B, She, Y, Gopalan, B, Miyagi, M, Stark, GR, and Lu, T*. PRMT5 dimethylates R30 of the p65 subunit to activate NF-kB. Proc Natl Acad Sci USA 110:13516-13521, 2013. *Corresponding Author. -1) Selected for F1000 Prime, 2) Hal Broxymeyer & Victoria Champion Outstanding Publication Award, 3) 2nd Place Award, Cancer Research Day
6. Lu, T*, Yang, M, Huang, D, Ghosh, G, and Stark GR. Role of lysine methyaltion of NF-kB in differential gene regulation. Proc Natl Acad Sci USA 110: 13510-13515, 2013. *Corresponding author - Selected for F1000 Prime
7. Zhang, T, Park, KA, Li, Y, Byun, HS, Jeon, J, Lee, Y, Hong, JH, Kim, JM, Huang, SM, Choi, SW, Kim, SH, Sohn, KC, Ro, H, Lee, JH, Lu, T, Stark, GR, Shen, HM, Liu, ZG, Park, J, and Hur, GM. PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65. Nat Commun 4:2062-2074, 2013.
8. Stark, GR, Wang, Y, and Lu, T. Lysine methylation of promoter-bound transcription factors and relevance to cancer. Cell Res 21(3):375-380, 2011.
9. Lu, T*, Jackson, MW, Wang, B, Yang, M, Chance, M, Miyagi, M, Gudkov, AV, and Stark, GR*. Regulation of NF-kB by NSD1/FBXL11-dependent reversible lysine methyaltion of p65. Proc Natl Acad Sci USA 107: 46-51, 2010 *Corresponding authors
10. Lu, T and Stark, GR. Use of forward genetics to discover novel regulators of NF-kB. Book Chapter in Book "NF-kB". Editors: Michael Karin and Lou Staudt, Cold Spring Harbor Press, p253-264, 2010.
Titles & Appointments
- Adjunct Assistant Professor of Biochemistry & Molecular Biology
- Adjunct Assistant Professor of Medical & Molecular Genetics
The research in my lab centers on the multi-functional transcription factor nuclear factor κB (NF-κB). As a hallmark in many cancers and a key link between inflammation and cancer, the pivotal transcription factor NF-κB is a “hot” target for disease treatment. My research focuses on addressing how NF-κB is regulated and how this regulation contributes to tumorigenesis. Ultimately, these studies may provide a rational basis for the design of new strategies for treating NF-κB-activated cancers and inflammatory disorders.
Two major directions of research are being conducted in our lab.
1) Epigenetic regulation of NF-κB in cancer.
We have discovered that the histone modifying enzymes, such as protein arginine methyltransferase 5 (PRMT5) and the F-box leucine repeat rich protein 11 (FBXL11), a known histone H3 lysine 36 (H3K36) demethylase are novel regulators of NF-κB. Currently, we are studying the role of these histone modifying enzymes in cancer. Specifically, we have adapted the AlphaLISA technique into a high throughput screen platform to screen for PRMT5 small molecule inhibitors. This work has resulted in two US Provisional Patents and one International Patent application. The lead compound and its derivatives may serve as the basis for new medicine development to combat cancer.
Furthermore, since elevated NF-κB activity has been widely observed in both chronic inflammatory bowel disease (IBD) and colitis-associated colon cancer (CAC), and is believed to be a key link between IBD and CAC, therefore, NF-κB is widely considered to be an attractive therapeutic target for CAC. We have successfully established genetically engineered mouse models to investigate the role of the role of FBXL11 in CAC and other inflammation related diseases, such as diabetes and atherosclerosis.
2) Using Validation-based insertional mutagenesis (VBIM) technique to discover novel genes.
VBIM is a powerful genetic approach for gene discovery. We have employed this innovative approach to identify novel regulators of NF-κB. These regulators may have great potential to serve as new biomarkers and therapeutic targets for cancer. Furthermore, understanding the underlying molecular mechanisms regarding how these novel regulators control NF-κB activity may help to devise innovative therapeutic strategies to control NF-κB activity in cancer.
Additionally, our lab is also utilizing VBIM technique to discover carboplatin and paclitaxel resistance genes in cancer. Once identified, targeting these genes may help to overcome chemoresistance to carboplatin or paclitaxel, thus, improving their efficacies for cancer treatment. Finally, the newly discovered drug resistance genes may serve as biomarkers to help physicians to design more precise treatment to each individual patient.
In conclusion, the research in our lab utilizes a broad range of advanced research techniques and experimental models to discover novel aspects of NF-κB regulation and new genes for drug resistance, with the hope of identifying innovative biomarkers, therapeutic targets in cancer and other NF-κB related diseases, and eventually, lead to the development of new medicines to treat these devastating diseases.
NIH-NIGMS Grant # 1R01GM120156-01A1
Role: Principle investigator
Project Title: Gene-specific responses to NF-κB through lysine and arginine methylation of p65
NIH-NCI Grant # 1 R03 CA223906-01
Role: Leading Principle Investigator (with Dr. Harikrishna Nakshatri)
Project Title: Impact of NF-κB methylation on chemoresistance and metastasis of breast cancer
V Foundation Kay Yow Cancer Fund 4486242
Role: Principle Investigator
Project Title: Facing the challenge, a novel approach to combat carboplatin resistance in ovarian cancer
100 VOH Grant # 2987613
Role: Leading Principle Investigator (with Dr. Lang Li)
Project Title: A novel approach to discover drug resistance genes in metastasized breast cancer cells
International Society of Interferon and Cytokine Research (ISICR)
International Cytokine Society (ICS)
American Association of Cancer Research (AACR)
Cancer Epigenetics Society (CES)
American Heart Association (AHA)