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Tao Lu, PhD

Assistant Professor of Pharmacology and Toxicology

Research Interest


The research in my lab centers on the multi-functional transcription factor nuclear factor κB (NFκB). As a hallmark in many cancers and a key link between inflammation and cancer, the pivotal transcription factor NFκB is a “hot” target for disease treatment. My research focuses on addressing how NFκB 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 NFκB-activated cancers and inflammatory disorders. 

Education

2003

Postdoctoral Fellow | Molecular Genetics
Cleveland Clinic 
Cleveland, OH 

2002

PhD | Molecular and Cell Biology
University of Toledo School of Medicine
Toledo, OH 

1994

M.S. | Biochemistry
Shandong University School of Medicine
PR China 

1991

B.S. | Biochemistry
Nanjing University
P.R. China 

Honors
 

2016

Trustees Teaching Award
Indiana University School of Medicine 

2015

Honorary Keynote Speaker
The Larry Gentry Researcy Forum 
University of Toledo School of Medicine 

2015

Elwert Award in Medicine
Indiana University 

2014

Young Investigator Travel Award
Internation Cytokine and Interferon Socity Conference 

2012

Walther Scholar
Indiana University
Walther Oncology Center

2009

First Place, ICS Young Investigator Award
Tri-Society [Society of Leukocyte Biology (SLB) &
ICS & ISICR] Conference 

2008

Seymour and Vivian Milstein
Young Investigator Award

International Society of Interferon & Cytokine
Research (ISICR) &
ICS Conference 

2007

Cleveland Clinic Innovator Award
Cleveland Clinic 

2007

Young Investigator Travel Award
International Cytokine Society (ICS) Conference 

2004

Young Investigator Travel Award
International Society of Interferon & Cytokine Research (ISICR) Conference 

2004

Cleveland Clinic Innovator Award
Cleveland Clinic 

1995

Distinguished Young Faculty Teaching Award
Shandong University School of Medicine        

Patent Applications

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.

The research in my lab centers on the multi-functional transcription factor nuclear factor κB (NFκB). Activation of NFκB, a central coordinator of immune responses, is tightly regulated in order to achieve its normal transient activation in response to stress. In some cancers, NFκB is activated abnormally, contributing to oncogenesis and tumor progression. Manipulating NFκB activity therefore, could be critical in the treatment of some subtypes of cancer. In order to control NFκB activity therapeutically, it is essential to understand the molecular control mechanisms that normally govern this transcription factor.


It is clear that regulation of transient NFκB activation is complex. We are still learning the details of how fine control is achieved.  At a molecular level, we are interested in finding novel post-translational modification sites of NFκB and studying how these modifications can modulate NFκB activity and gene regulation, as well as the downstream biological consequences. In a broader range, we are interested in using a validation-based insertional mutagenesis (VBIM) technique (Ref.1) to screen for unknown regulators of NFκB and further investigating the molecular mechanisms of how these factors modulate NFκB activity. We expect this research to lead to new strategies for the prevention and treatment of cancer.  

Adopted from: www.cellsignal.com


We have found that the histone modifying enzymes, such as protein arginine methyltransferase 5 (PRMT5) (Ref.2, 3) and the F-box leucine repeat rich protein 11 (FBXL11), a known histone H3 lysine 36 (H3-K36) demethylase (Ref. 4, 5) are novel regulators of NFκB. Currently, we are studying the role of these histone modifying enzymes in cancer. Furthermore, since elevated NFκB 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, NFκB is considered to be an attractive therapeutic target for CAC. We are interested in studying the role of FBXL11 or PRMT5 in CAC in genetically modified murine models. We expect this important research will greatly advance our knowledge of colon cancer prevention and anti-cancer drug development. Similar experiments would be done for other novel NFκB regulators that will be identified by using the VBIM technique.  


Summary  

As a hallmark in many cancers and a key link between inflammation and cancer, the pivotal transcription factor NFκB is a “hot” target for disease treatment. My research focuses on addressing how NFκB 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 NFκB-activated cancers and inflammatory disorders. Moreover, VBIM has been validated extensively as a powerful tool for gene discovery that could have broad applications in many different systems.  


References   

1.  Lu, T and Stark, GR. (2009). Use of forward genetics to discover novel regulators of NFkB. Book Chapter in Book “NFkB”, Editors: Michael Karin and Lou Staudt, Cold Spring Harbor Press, p253-264.

2.  Wei, H, Wang, B, She, Y, Gopalan, B, Miyagi, M and Lu, T. (2013). PRMT5 dimethylates R30 of the p65 subunit to activate NFkB. Proc. Natl. Acad. Sci. 110 (33):13516-13521. Corresponding author. Selected as Indiana University Simon Cancer Center (IUSCC) Outstanding Publication.

3.  Wei, H, Mundade, R, Lange, KC and Lu, T. (2014). Protein arginine methylation of non-histone proteins and its role in diseases. Cell Cycle 13: 32-41. Corresponding author.

4.  Lu, T*, Jackson, MW, Singhi, AD, Kandel, ES, Yang, M, Gudkov, AV, and Stark, GR*. (2009). Validation-based insertional mutagenesis to identify the FBXL11 as a negative regulator of NFkB. Proc Natl  Acad Sci USA, 106:16339-1634.  * Corresponding authors.

5.  Lu, T*, Jackson, MW, Wang, B, Yang, M, Chance, M, Miyagi, M, Gudkov, AV, and Stark, GR*. (2010). Regulation of NFkB by NSD1/FBXL11-dependent reversible lysine methylation.

 


Select Publications

Tao Lu Lab

Han Wei, Ph.D.

Research Associate

weihan@iupui.edu

Dr. Han Wei received her Ph.D. from Graduate University of Chinese Academy of Sciences where she studied the biological effects of urban fine particulate matters (PM2.5) on the cardiovascular system and NF-κB signaling pathway related gene expression. In Dr. Tao Lu’s lab, Han’s research mainly focuses on investigating the role of novel posttranslational modifications of  NF-κB and its role in cancer and other NF-kB-driven diseases. Additionally, Han is also involved in a drug resistance study in women cancers. 

Antja-Voy graduated with a BS in Biological Sciences from Oakwood College. From there, she gained invaluable experience at the University of Alabama in Huntsville and Emory University, where she focused on Fungal Pathogenesis and HIV-1 pseudotyping. In Dr. Lu’s lab, her research focuses on investigating the role of novel posttranslational modifications of NF-kB regulators and using mouse models to determine the role of NF-kB regulating enzymes in colitis-associated colorectal cancer. 

Matthew Martin received his bachelor’s degree in biology from Purdue University where he studied tyrosine kinase inhibitor resistance in TKI resistant CML lines. He also studied the effects of the neural microenvironment on astrocyte and neuron signaling at IUPUI. In Dr. Tao Lu’s lab, Matthew’s research is focused on using novel cell-based approaches to identify drug resistance and drug sensitivity genes in breast cancers.  

Lakshmi entered the IBMG program at IUSM in the Fall of 2013 and joined the Lu Lab in summer of 2014. She completed her MS in Cell and Molecular Biology with research work in the Bernstein Lab at San Diego State University and her BS in Biotechnology from Mithibai College, University of Mumbai. As part of her PhD thesis project in the Lu lab, Lakshmi is working on understanding the role of protein arginine methyltransferase 5 (PRMT5) in pancreatic cancer.

Awards
 

Name

Award

Agency

Year

Lakshmi Prabhu
PhD Candidate 
 

Paradise Travel Award
 

Department of Pharmacology & Toxicology

2015

 

Han Wei, PhD



Cancer Research Day
Basic Science 2nd Place


IU Simon Cancer Center


2014


 

Han Wei, PhD


 



Hal Broxmeyer & Victoria Champion Award for Outstanding Publication in Cancer Research  

IU Simon Cancer Center




2014





Rasika Mundade, MS



Paradise Travel Award



Department of Pharmacology & Toxicology

2014



Rasika Mundade, MS



American Cancer Assoc. Research Travel Award
 

IU Simon Cancer Center


2014


 

Alumni
 

Larry L. Hua, Ph.D.

Rasika Mundade, M.S.

Yun She, M.S.

Fatima Warsame, M.S./M.D. Student


Department of Pharmacology and Toxicology | 635 Barnhill Drive, MS A401 | Indianapolis, IN 46202