Timothy S. Pardee

Assistant Professor of Internal Medicine, Section on
     Hematology and Oncology 

B.S., 1993 University of Buffalo 
Ph.D., 1999 University of Buffalo 
M.D., 2003 University of Buffalo 

My lab is focused on developing a better understanding of Acute Myeloid Leukemia (AML). AML is an aggressive malignancy of the bone marrow where the white blood cells that usually protect us from infections become cancerous, leading to bone marrow failure and death. This cancer is characterized by a high relapse rate and resistance to chemotherapy. It has long been known that different genetic changes present in the leukemia cells can predict how well they will respond to therapy and how likely a patient is to achieve a lasting remission. This information is currently used to provide prognosis and direct therapy however, the mechanisms of how these genetic changes influence the way the cells respond to chemotherapy are not well understood.

To address these questions we utilize several mouse models of AML that incorporate genetic changes found in the human disease. One model uses a fusion protein found in good risk AML (AML-ETO9a) and the other a fusion from poor risk AML (MLL-ENL). These models accurately recapitulate the pathology of the disease and more importantly when mice are treated with the same chemotherapy regimes as patients the outcomes are similar. These models are based on the infection of hematopoetic stem cells with retroviruses that can be engineered to express any gene of interest. In this way different genes implicated in altering prognosis for AML patients can be incorporated into these models and their effects on chemotherapy response can be assessed.

We are currently using these models to assess how common genetic changes seen in AML effect disease onset and response to chemotherapy. The ultimate goal of this work is to better understand the mechanisms of resistance in AML and to design strategies to reverse it. Any promising findings can then be used to inform clinical trials and improve care for patients who suffer from this devastating disease.

Recent Publications (selected):

1.      Zuber, J. Radtke, I. Pardee, TS. Zhao, Z. Rappaport, A.R. Luo, W. McCurrach, M. Yang, M. Kogan, S.C. Downing, J.R. and Lowe, S.W. Mouse models of human AML accurately predict chemotherapy response. Genes and Development. 2009 Apr 1;23(7):877-89.

2.      Berger-Zaslav AL. Spitzer S. Mercado T. Richard S. Pardee TS. Knorr E. Tully D. and Zamkoff K. Further Evidence of Poor Prognosis For Ph-CML Patients with Deletions of the Derivative Chromosome 9 on Imatinib Therapy. Cancer Genetics and Cytogenetics. Submitted. 

3.      Pardee TS. Hagag N. Singh B. Zamkoff K. Gladstone D.   Effective CD34+ Stem Cell Mobilization with Low-dose Pegfilgrastim. The Journal of Applied Research in Clinical and Experimental Therapeutics. 6(3): 196-200, 2006. 

4.      Pardee TS. Ghazy MA. Ponticelli AS. Yeast and Human RNAPII Elongation Complexes: Evidence for Functional Differences and Post Initiation Recruitment of Factors. Eukaryotic Cell. 2(2): 318-327, 2003 April.

5.      Pardee TS. Bangur CS. Ponticelli AS. The N-terminal region of yeast TFIIB contains two adjacent functional domains involved in stable RNA polymerase II binding and transcription start site selection. Journal of Biological Chemistry. 273(28):17859-64, 1998 Jul 10.

6.      Bangur CS. Pardee TS. Ponticelli AS. Mutational analysis of the D1/E1 core helices and the conserved N-terminal region of yeast transcription factor IIB (TFIIB): identification of an N-terminal mutant that stabilizes TATA-binding protein-TFIIB-DNA complexes. Molecular & Cellular Biology. 17(12):6784-93, 1997 Dec.

7.      Ponticelli AS. Pardee TS. Struhl K. The glutamine-rich activation domains of human Sp1 do not stimulate transcription in Saccharomyces cerevisiae. Molecular & Cellular Biology. 15(2):983-8, 1995 Feb.