• Associate Professor of Pediatrics
• Associate Professor of Microbiology and Immunology
• Director, Pediatric Pulmonary Basic Research
• Associate Member of the Walther Oncology Center

• Campus Address: RI 2612A
• Telephone: (317) 278-3696
• E-mail: mkaplan2@iupui.edu

Hal Broxmeyer named distinguished professor at IUSM (click here for more details)

Janice Blum discusses Immunology & Infectious Diseases (click here for more details)

Training:
• B.Sc., 1987: University of Windsor, Canada
• Ph.D., 1992. WayneStateUniversity, Detroit, MI
• Post Doctoral, 1992-1995: University of Texas Southwestern Medical Center
• Post Doctoral, 1995-1997: HarvardUniversitySchool of Public Health

Area of research:
Regulation of genes and cellular phenotypes in the immune response; STAT protein immunobiology; T helper cell regulation and function.

Description and summary of research focus of the laboratory:
One area of Dr. Kaplan’s research is focused on studying the immunobiology of STAT proteins. STAT (Signal Transducer and Activator of Transcription) proteins are a class of molecules involved in signaling from the cytokine receptor directly to the nucleus, where they bind DNA and alter gene transcription. We have developed mice that are deficient in Stat4 or Stat6, factors involved in signaling for IL-12 and IL-4, respectively. In the absence of Stat4, cells are unable to respond to IL-12 by proliferating, producing IFN g and becoming effective Th1 cells. Similarly, Stat6-deficient mice lack the ability to modulate many surface markers, proliferate or become Th2 cells in response to IL-4.These studies demonstrated that STAT proteins perform non-redundant and crucial roles in cytokine signaling. We have further generated mice transgenic for mutant forms of Stat4 and Stat6 and crossed them back to wild-type and gene-deficient backgrounds. These mice will be very useful in determining how Stat4 and Stat6 function in the immune system, and regulate inflammatory and atopic disease processes. Future work will focus on understanding how STAT proteins regulate immunological functions and cytokine responses at the cell and molecular level in vitro and in vivo.

Poxviruses are a class of double-stranded DNA viruses that cause several diseases including smallpox and monkey pox. In a concerted effort with several other investigators, Dr. Kaplan’s laboratory and Dr. Michael Klemsz’ laboratory are examining the function of a poxvirus protein, VH1, which functions as a phosphatase and inhibits STAT signaling. We are comparing the function of VH1 from different poxviruses to determine if they have specific functions in each virus. This will help us to understand how poxviruses evade host immunity in an effort to better be able to treat poxvirus infection.

A final project, also a collaboration with Dr. Klemsz’ laboratory, examines how the transcription factor PU.1 contributes to the Th2 phenotype. We have determined that PU.1 can modulate the Th2 phenotype by interacting with GATA-3, the master regulator of Th2 commitment. However, PU.1 is only expressed in subsets of Th2 cells suggesting that it contributes to a heterogeneous population phenotype and may dictate specific functions within the Th2 phenotype.

Publications
Broxmeyer HE, Bruns HA, Zhang S, Cooper S, Hangoc G, McKenzie AN, Dent AL, Schindler U, Naeger LK, Hoey T, and Kaplan MH . (2002) Th1 cells regulate hematopoietic progenitor cell homeostasis by secretion of Oncostatin M. Immunity. 16:815-825.

Bruns HA, Schindler U and Kaplan MH . (2003) Expression of a constitutively active Stat6 in vivo alters lymphocyte homeostasis with distinct effects in T and B cells. J Immunol. 170:3478-3487.

Chang H-C, Zhang S, Oldham IL, Naeger L, Hoey T and Kaplan MH. (2003) The Stat4 N-terminal domain is required for efficient phosphorylation. J. Biol Chem. 278:32471-32477.

Hoey T, Zhang S, Schmidt N, Yu Q, Ramchandani S, Xu X, Naeger LK, Sun Y-L, and Kaplan MH. (2003) Distinct requirements for naturally occurring splice forms Stat4 a and Stat4 b in IL-12 responses. EMBO J. 22:4237-4248.

O'Sullivan AC, Chang H-C, Yu Q and Kaplan MH. (2004) STAT4 is required for IL-12 induced chromatin remodeling of the CD25 locus. J Biol Chem. 279:7339-7345.

Search Pub Med (narrow search by entering: Kaplan MH AND (stat4 OR stat6 or stat3 or stat1 or PU.1 or IL-4 or IL-12 or IL-13 or Bright) in the search window after "for"

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