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Faculty Detail    
Name JIANMEI WU LEAVENWORTH
MD PhD
 
Campus Address CHB 130
Phone  (20-5) -880
E-mail  jleavenworth@uabmc.edu
Other websites http://labs.uab.edu/jwleaven/
     

Education
Medical School  Nantong University    2001  MD 
Graduate  Southern Illinois University    2009  PhD 
Graduate  Dana-Farber Cancer Institute; Havard Medical School    2013  Postdoctoral Fellow 


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurosurgery   Neurosurg-Laboratory Research Assistant Professor
Secondary  Microbiology  Microbiology Assistant Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Assistant Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Assistant Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Assistant Professor
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Assistant Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Immunology 
Medical Scientist Training Program 
Microbiology 
Molecular and Cellular Pathology Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Leavenworth joined UAB Neurosurgery as an Assistant Professor on Oct. 1, 2016. Previously, Dr. Leavenworth was at the Dana-Farber Cancer Institute at Harvard University. Her main research interest is to understand the mechanisms of self-tolerance, focusing on molecular and cellular elements that regulate effector and regulatory cell subsets of the immune response. Her long-term goal is to seek effective strategies for cancer immunotherapy using mouse models and specimens from patients with malignant tumors, including gliomas. Dr. Leavenworth completed medical school at Nantong University (NTU) School of Medicine, China. She then finished her PhD training in molecular biology, microbiology and biochemistry with a focus on immunology at Southern Illinois University School of Medicine. She was at Harvard Medical School since 2009 serving as a research fellow (Postdoc) and then as an instructor.

Society Memberships
Organization Name Position Held Org Link
Society for Immunotherapy of Cancer     
American Association for Cancer Research     
The Society for Natural Immunity     
American Association of Immunologists     
Federation of Clinical Immunology Societies     



Research/Clinical Interest
Title
Cancer-Immune cell Crosstalk: Discovery of new targets for cancer immunotherapy
Description
A major goal of our research is to seek effective strategies for cancer immunotherapy, focusing on the definition and manipulation of effector and regulatory subsets within the tumor microenvironment. There are 3 ongoing projects: 1) The contribution of regulatory T cell subsets to tumor development. The tumor microenvironment is highly immunosuppressive, representing one of the common hurdles that prevent an effective approach to cancer immunotherapy. Regulatory T cells (Tregs) are critical initiators and amplifiers of the immunosuppression. Not only do they directly repress effector cells that attack the tumor, but they are also expanded by the other suppressors - such as myeloid derived suppressor cells (MDSC) and tumor associated macrophages (TAM) - to intensify the immunosuppression and to enhance tumor growth. The identity, stability, and function of Tregs within the tumor remain largely unclear. We will a) characterize Treg cell subsets within the tumor microenvironment; b) evaluate approaches to modify these Treg cell subsets to induce enhanced antitumor immunity. 2) The contribution of NK cell subsets to antitumor responses. Current efforts in immunotherapy have focused mainly on enhancing T-cell responses to tumors. Less is discussed regarding how to mobilize other effector cells, such as NK cells, to mediate cooperative antitumor responses. Although NK cells, a component of innate immunity, are endowed with tumor-killing activity, and often correlate with the prognosis of cancer patients, relatively limited insight into NK cell biology has impeded NK cell–based therapeutic approaches. We will a) delineate the contribution of genetic and epigenetic regulation to NK cell function and to NK cell adaptive responses; b) characterize NK cell adaptive responses to tumors and evaluate approaches that can enhance such responses. 3) The impact of oncolytic HSV-based therapy on antitumor immune responses. This is a collaborative project among immunologists, neurologists and neurosurgeons at UAB. Using mouse models and specimens from patients with malignant brain tumors pre- and post-treatment with a replication conditional oncolytic HSV (oHSV), we will characterize the impact of oHSV therapy on the immune responses systemically and within the tumor, to seek biomarkers for the improved outcome and design combined approaches to enhance antitumor responses.

Selected Publications 
Publication PUBMEDID
Yin J*, Leavenworth JW*,#, Li Y, Luo Q, Xie H, Liu X, Huang S, Yan H, Fu Z, Zhang LY, Zhang L, Hao J, Wu X, Deng X, Roberts CW, Orkin SH, Cantor H#, Wang X#. Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity. Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):15988-93. (*co-first author; #co-corresponding author).  26668377 
Leavenworth JW, Verbinnen B, Yin J, Huang H, Cantor H. A p85α–osteopontin axis couples the ICOS receptor to sustained Bcl-6 expression by follicular helper and regulatory T cells. Nature Immunol. 2015 Jan;16(1): 96–106.   25436971 
Li Y, Yin J, Li T, Huang S, Yan H, Leavenworth J#, Wang X#. NK cell-based cancer immunotherapy: from basic biology to clinical application. Sci China Life Sci. 2015 Dec;58(12):1233-45. (#co-corresponding author).  26588912 
Leavenworth JW, Verbinnen B, Wang Q, Shen E, Cantor H. Intracellular osteopontin regulates homeostasis and function of natural killer cells. Proc Natl Acad Sci U S A. 2015 Jan 13;112:494-9.   25550515 
Albertsson AM, Zhang X, Leavenworth J, Bi D, Nair S, Qiao L, Hagberg H, Mallard C, Cantor H, Wang X. The effect of osteopontin and osteopontin-derived peptides on preterm brain injury. J Neuroinflammation. 2014 Dec 3;11(1):197.  25465048 
Albertsson AM, Bi D, Duan L, Zhang X, Leavenworth JW, Qiao L, Zhu C, Cardell S, Cantor H, Hagberg H, Mallard C, Wang X. The immune response after hypoxia-ischemia in a mouse model of preterm brain injury. J Neuroinflammation. 2014 Sep 5;11(1):153.   25187205 
Leavenworth JW, Tang X, Kim HJ, Wang X, Cantor H. Amelioration of arthritis through mobilization of CD8+ regulatory T cells. J. Clin Invest. 2013; 123: 1382-9.   23376792 
Leavenworth JW, Wang X, Wenander CS, Spee P, Cantor H. Mobilization of natural killer cells inhibits development of collagen-induced arthritis. Proc Natl Acad Sci U S A. 2011;108:14584-9. (Research Highlight, Nat Rev Rheumatol. 2011; 7: 622. PMID: 22009332.)  21873193 
Leavenworth JW, Schellack C, Kim HJ, Lu L, Spee P, Cantor H. Analysis of the cellular mechanism underlying inhibition of EAE after treatment with anti-NKG2A F(ab')2. Proc Natl Acad Sci U S A. 2010;107:2562-7.   20133787 
Leavenworth JW, Ma X, Mo YY, Pauza ME. SUMO conjugation contributes to immune deviation in nonobese diabetic mice by suppressing c-Maf transactivation of IL-4. J Immunol. 2009;183:1110-9.   19553542 
Leavenworth JW, Pauza ME. Engagement of transgenic Ly49A inhibits mouse CD4 cell activation by disrupting T cell receptor, but not CD28, signaling. Cell Immunol. 2009;257:88-96.   19362713 
Peng S, Lalani S, Leavenworth JW, Ho IC, Pauza ME. c-Maf interacts with c-Myb to down-regulate Bcl-2 expression and increase apoptosis in peripheral CD4 cells. Eur J Immunol. 2007;37(10):2868-80.   17823980 

Keywords
Immunology, Cancer Immunology, Immunotherapy, Treg, NK cells, glioma