Faculty Profile

 


Dr. Thomas Kipps
Dr. Kipps

Thomas Kipps, M.D., Ph.D.

Professor of Medicine

Division of Hematology-Oncology

Deputy Director for Research

UC San Diego Moores Cancer Center

 

Office Address:

Division of Hematology-Oncology

University of California, San Diego

Moores Cancer Center

3855 Health Sciences Drive, MC-0820

La Jolla, CA 92093

tkipps@ucsd.edu
Office: (858) 534-5400
FAX:(858) 534-5620


Education and Training

BA Biochemistry, Columbia University 1971-1974
MD, PhD (Immunology), Harvard Medical School 1974-1979
Residency Stanford University 1979-1982
Fellowship Hematology & Genetics, Stanford University 1982-1985

Biography

Thomas Kipps, MD, PhD, is Professor of Medicine, Evelyn and Edwin Tasch Chair in Cancer Research, and Deputy Director of Research Operations at the UC San Diego Moores Cancer Center. He received his Ph.D. in Immunology and M.D. from Harvard University and had his residency and fellowship training in Internal Medicine, Hematology, and Genetics at Stanford University.

Dr. Kipps has a national and international reputation for his work in cancer research, immunology, and gene therapy. He has been a leader in the field for many years, and has helped to develop standardized treatment protocols. He is the author of more than 300 publications and is the PI on several peer-reviewed grants, including an award from NCI/NIH to fund the Chronic Lymphocytic Leukemia Research Consortium (CRC). The CRC involves collaboration with eight other Cancer Centers around the United States and the UK. Dr. Kipps is also the Director of the Blood Cancer Research Fund at the UC San Diego Moores Cancer Center. The Blood Cancer Research Fund concentrates on developing cures for all types of blood related cancers, specifically Chronic Lymphocytic Leukemia (CLL).

Dr. Kipps has over 20 years’ experience in combining research and clinical care responsibilities.
As deputy director of research operations, Dr. Kipps is working to further integrate basic and translational research investigators at the Moores Cancer Center with clinical investigators, epidemiologists, and physicians offering state-of-the art therapies for patients with various forms of cancer.

Research Interests

A major focus of Dr. Kipps’ research is the immunobiology and genetics of human B-cell malignancies, with emphasis on chronic lymphocytic leukemia (CLL). Dr. Kipps’ work has provided insight into the ontogeny of B cells that are subject to leukemia transformation and defined the highly restricted nature of the immunoglobulins expressed in this disease. In addition, he has defined genetic factors that contribute to the development and progression of this disease, identified biochemical pathways that enhance the growth or survival of leukemia B cells, identified means with which to elicit host anti-leukemia immune responses through vaccines generated via gene transfer, and identified promising new drugs and biologic agents that have activity in the treatment of this disease. He has made seminal observations on how the microenvironment can promote survival of CLL cells and defined strategies for mitigating the protective effects of the microenvironment on CLL cells survival in vivo. He has instigated and enabled work on selected leukemia cell samples of patients with sporadic or familial CLL that led to discovery of the role played by microRNA and ultraconserved, non-coding RNAs in the pathogenesis or progression of CLL in collaborations with the laboratory of Dr. Carlo Croce of the CLL Research Consortium (CRC). In other collaborations initiated through the CRC, Dr. Kipps also contributed to work on the epigenetic factors that contribute to pathogenesis in CLL.

The study on CLL cells serially collected from patients at time points before therapy, during therapy, or after relapse from therapy allows for investigation of the genetic and biologic features associated with tumor progression, therapeutic response, or resistance to therapy. Discovery of features that distinguish CLL from their normal cell counterparts has helped identify new targets for therapy and/or define surrogate markers associated with more rapid rates of cancer progression or resistance to standard therapy. These studies are integrated with a clinical investigative program that attracts patients seeking improved modalities of treatment for CLL. From this, Dr. Kipps has identified molecular markers that can segregate patients into subgroups that have different risks for disease-progression or different probabilities of response to conventional treatment. This also has allowed for testing the safety and relative efficacy of novel agents developed for treatment of all patients with CLL or subgroups of patients hypothesized to have the best potential response to novel forms of therapy.

Most recently, Dr. Kipps has discovered that the embryonic antigen ROR1 is expressed on CLL. ROR1 an embryonic type I membrane receptor tyrosine kinase-like surface protein. ROR1 was not expressed on normal, healthy adult tissues, but was found on the leukemia cells of virtually all cases of CLL and on the neoplastic cells of many patients with solid tumors. His work has demonstrated that patients immunized with autologous CLL cells transfected to express the CD40-ligand (CD154) can generate antibodies that are specific for this type I tyrosine kinase that apparently can block its capacity to function as a survival receptor for wnt5a. This work potentially could lead to development of novel vaccines for patients with this disease. Currently, Dr. Kipps is collaborating with other investigators at the UC San Diego Moores Cancer Center on developing monoclonal and recombinant antibodies specific for ROR1 and have identified one that can interfere with ROR1 signaling. The California Institute of Regenerative Medicine (CIRM) is funding this work.

Another project undertaken in the Kipps’ lab is to define the nature of immunoglobulin gene expression in normal and neoplastic B cells and to examine the relationship between B-cell receptor signaling events and mechanisms governing the pathogenesis and/or progression of CLL. In addition he is investigating the role of the microenvironment in support both normal and neoplastic B cell survival. In addition to his laboratory research, Dr. Kipps is actively involved in clinical research; having developed and/or conducted several phase I and phase II clinical trials.

Publications

Castro JE, James DF, Sandoval-Sus JD, Jain S, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia 2009; 23 (10):1779-1789.

Visone R, Rassenti LZ, Veronese A, Taccioli C, Costinean S, Aguda BD, Volinia S, Ferracin M, Palatini J, Balatti V, Alder H, Negrini M, Kipps TJ, Croce CM. Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood. 2009 Oct 29;114(18):3872-9.

Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, Dyer MJ, Padmanabhan S, Piotrowska M, Kozak T, Chan G, Davis R, Losic N, Wilms J, Russell CA, Osterborg A; Hx-CD20-406 Study Investigators. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010. 1;28(10):1749-55.

Wierda WG, Castro JE, Aguillon R, Sampath D, Jalayer A, McMannis J, Prussak CE, Keating M, Kipps TJ. A phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154. Leukemia. 2010 Nov;24(11):1893-900.

Zhang W, Kater AP, Widhopf GF, 2nd, Chuang HY, Enzler T, James DF, Poustovoitov M, Tseng PH, Janz S, Hoh C, Herschman H, Karin M, Kipps TJ. B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2010 Nov 2;107(44):18956-60.

Messmer D, Fecteau JF, O'Hayre M, Bharati IS, Handel TM, Kipps TJ. Chronic lymphocytic leukemia cells receive RAF-dependent survival signals in response to CXCL12 that are sensitive to inhibition by sorafenib. Blood. 2011;117(3):882-9.

Visone R, Veronese A, Rassenti LZ, Balatti V, Pearl DK, Acunzo M, Volinia S, Taccioli C, Kipps TJ, Croce CM. miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood. 2011 Sep 15;118(11):3072-9.

Steininger C, Widhopf GF, 2nd, Ghia EM, Morello CS, Vanura K, Sanders R, Spector D, Guiney D, Jager U, Kipps TJ. Recombinant antibodies encoded by IGHV1-69 react with pUL32, a phosphoprotein of cytomegalovirus and B-cell superantigen. Blood 2012 Mar 8;119(10):2293-301.

Zhang S, Chen L, Cui B, Chuang HY, Yu J, Wang-Rodriguez J, Tang L, Chen G, Basak GW, Kipps TJ. ROR1 Is Expressed in Human Breast Cancer and Associated with Enhanced Tumor-Cell Growth. PLoS One2012;7(3):e31127.

Castro JE, Melo-Cardenas J, Urquiza M, Barajas-Gamboa JS, Pakbaz RS, Kipps TJ. Gene immunotherapy of chronic lymphocytic leukemia: a Phase I study of intranodally injected adenovirus expressing a chimeric CD154 molecule. Cancer Res. [epub 2012 Apr 17].

Chuang HY, Rassenti L, Salcedo M, Licon K, Kohlmann A, Haferlach T, et al. Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression. Blood. 2012.

Laboratory

Laboratory test tubes.

 

Laboratory Personnel
Name Title Laboratory Focus
Liguang Chen Project Scientist Protein expression and signal transduction in CLL

Laura Rassenti

Project Scientist

Molecular genetic analyses of immunoglobulins expressed in chronic lymphocytic leukemia & normal B cells. Analyze prognostic markers for CLL. Director of the Tissue Core for the CRC
George Widhopf Project Scientist Molecular characterization of immunoglobulin expressed by normal and leukemic B lymphocytes; Development of monoclonal antibodies & peptide vaccines against CLL
Emanuela Ghia Project Scientist Molecular characterization of immunoglobulin genes expressed in chronic lymphocytic leukemia. Mutation screening of important genes in chronic lymphocytic leukemia using longitudinal samples. Gene expression analysis.
Suping Zhang Postdoctoral Fellow Targeted therapy in CLL and signal transduction in cancer
Masato Obara Postdoctoral Fellow Impact of gene mutations in CLL
Maria Schwaederle Postdoctoral Fellow Impact of gene mutations in CLL
Marek Mraz

Postdoctoral Fellow

Role of non-coding RNA’s in CLL
Jian Yu Postdoctoral Fellow Development of monoclonal antibodies & peptide vaccines against CLL
Jessie Fecteau Postdoctoral Fellow CLL microenvironment & immunotherapy
Bing Cui Postdoctoral Fellow Gene therapy and immunotherapy studies in CLL