Mark Levis, M.D., Ph.D.

Assistant Professor of Oncology and Hematology Contact Information: To Make an Appointment: New Patients: 410-955-4116 Return Patients: 410-955-8895 Administrative Office: 410-955-4116 Fax: 410-614-7279

Clinical/Academic Interests:

Acute leukemia; Aggressive/high-grade Lymphoma

Research Interests:

Dr. Levis’ laboratory research focuses on the development of molecularly targeted therapies for leukemia.  Currently, he is actively involved in the pre-clinical and clinical development of small molecule inhibitors of the receptor tyrosine kinase, FLT3.  The research involves studying the biochemical effects of these inhibitors on primary blast samples from leukemia patients.  In addition, the NOD/SCID mouse is used as a model system to study the leukemia stem cell and its response to FLT3 inhibitors.

Education:

A.B., 1984, University of California, Berkeley.  Genetics.

Ph.D. in Biochemistry awarded 1992; University of California, San Francisco.

M.D., awarded June 1994; University of California, San Francisco.

Post-Doctoral Training:

Residency in Internal Medicine, completed June, 1997, Osler Medical Service at Johns Hopkins, Baltimore, MD.

Fellowship in Medical Oncology, July 1999 to June, 2002, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.

Academic Positions:

Clinical Instructor, Department of Medicine, Union Memorial Hospital, Baltimore, MD, 1997-1998.

Assistant Chief of Service, Osler Medical Service, Johns Hopkins University, Baltimore, MD, 1998-1999.

Assistant Professor of Oncology, Johns Hopkins University, 2002-Present.

Selected References:

1. Levis, M., Tse, K-F., Smith, B.D., Garrett, E., and Small, D. (2001).  A FLT3 tyrosine kinase inhibitor is cytotoxic to AML blasts harboring a FLT3/ITD mutation.  Blood. 98:885.
   
   
2. Levis, M., Allebach, J., Tse, K-F., Sheng, R., Baldwin, B.R., Smith, B.D., Jones-Bolin, S., Ruggeri, B., Dionne, C., and Small, D. (2002).  A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo.  Blood  99:3885.
   
   
3. Smith, B.D., Levis, M., Beran, M., Giles, F., Brown, P., Russell, L., Hellriegel, E., Murphy, K., Dauses, T., Allebach, J., and Small, D. (2004) Single agent CEP-701, a novel FLT3 inhibitor, shows initial response in patients with refractory acute myeloid leukemia. Blood. 103:3669
   
   
4. Levis, M. and Small, D.  (2003).  FLT3:ITDoes matter in leukemia.  Leukemia.  17:1738.
   
   
5. Murphy, K.M., Levis, M., Hafez, M.J., Geiger, T., Cooper, L.C., Smith, B.D., Small, D., and Berg, K.D.  (2003).  Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assay.  J Mol Diagn.  5: 96-102.
   
   
6. Zheng, R., Levis, M, Piloto O, Brown P, Baldwin B., and Small, D. (2003) FLT3 ligand (FL) causes autocrine signaling in AML cells. Blood.  103:267.
   
   
7. Levis, M., and Small, D.  (2004).  Small molecule FLT3 tyrosine kinase inhibitors.  Current Pharmaceutical Design.  10:1183.
   
   
8. Zheng, R., Levis, M., Li, L., Friedman, A., and Small, D. (2003).  Internal Tandem Duplication Mutation of FLT3 Blocks Myeloid Differentiation Through Suppression of C/EBPa Expression.  Blood. 103:1883.
   
   
9. Levis, M., Pham, R., Smith, B.D., and Small, D. (2004).  In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important in order to achieve synergistic cytotoxic effects.  Blood. 104:1145.
   
   
10. Levis, M., and Small, D. (2004).  Kinase Inhibitors in Leukemia.  Advances in Pharmacology 51:1-33.
    
    
11. Levis, M.  (2004). CXCR-4: homing in on FLT3.  Blood. 104: 303-304.
    
    
12. Levis, M., Murphy, K.M., Pham, R., Kim, K.T., Stine, A., Li, L., McNiece, I., Smith, B.D., and Small, D.  (2005). Internal tandem duplications of the FLT3 gene are present in leukemia stem cells. Blood 106(2):673-80.
    
    
13. Brown, P., Levis, M., Shurtleff, S., Campana, D., Downing, J., and Small, D. (2005).  FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression.  Blood 105:812.
    
    
14. Kim KT, Baird K, Ahn JY, Meltzer P, Lilly M, Levis M, and Small D. (2005). Pim-1 is upregulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival.  Blood. 105 (4):1759-67.
    
    
15. Chen P, Levis M, Brown P, Kim KT, Allebach J, Small D.  (2005).  FLT3/ITD mutation signaling includes suppression of SHP-1. FLT3/ITD mutation signaling includes suppression of SHP-1.  J. Biol. Chemistry.  280 (7):5361-9.
    
    
16. Piloto, O., Levis, M., Huso, D., Li, Y., Li, H., Wang, M-N., Bassi, R., Balderes, P., Ludwig D.L., Witte, L., Zhu, Z., Kicklin, D.J., and Small, D.  (2005).   Inhibitory Anti-FLT3 antibodies are capable of mediating Antibody-dependent cell-mediated cytotoxicity and reducing engraftment of acute myelogenous leukemia blasts in nonobese diabetic/severe combined immunodeficient mice.  Cancer Research 65: 1514.
    
    
17. Levis, M. (2005). Recent advances in the development of small molecule inhibitors for the treatment of acute myeloid leukemia.  Current Opinion in Hematology.  12:55.