Faculty Detail   
Name JEREMY B FOOTE
Director of Comparative Pathology Lab
Director of the Gnotobiotic Mouse Core 		 
Campus Address RSB 250- Zip 2800
Phone  (205) 975-0688
E-mail  jbf130@uab.edu
Other websites Bibliography-Complete List of Publications
    

 Education

Undergraduate  Pennsylvania State university    2002  B.Sc. Biochemistry and Molecular Biology 
Graduate  University of Alabama at Birmingham    2009  Ph.D. in Microbiology and Immunology 
Medical School  Auburn University, College of Veterinary Medicine    2013  D.V.M 
Residency  Johns Hopkins School of Medicine, Department of Molecular and Comparative Pathobiology    2017  DACVP 

 Certifications

Diplomate of the American College of Veterinary Pathologists  2017 

Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Microbiology  Microbiology Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor
Center  Ctr for Clinical & Translational Sci  Ctr for Clinical & Translational Sci Associate Professor
Center  Nutrition Sciences Research  Nutrition Obesity Res Ctr (NORC) Associate Professor
Center  UAB Immunology Institute  UAB Immunology Institute Associate Professor

Biographical Sketch 
I performed my undergraduate studies in biochemistry and molecular biology at Pennsylvania State University (B.Sc, 2002). For graduate studies I trained with John Kearney, Ph.D. at the University of Alabama at Birmingham (Birmingham, AL). My thesis research focused on understanding the development of serologic and B cell memory to the T cell independent, type 2 antigen alpha 1->3-dextran. After obtaining my Ph.D. in microbiology and immunology, I took a 4 year hiatus from research to obtain my doctorate in veterinary medicine at Auburn University, College of Veterinary Medicine. While at Auburn I obtained additional training in cancer genetics and immunology under the guidance of Dr. Curtis Bird, Ph.D. My research in Dr. Bird’s lab focused on generating a mouse model of the canine immune system, permissible to engraftment of canine peripheral blood mononuclear cells derived from canine patients with mammary cancer. The goal of this work was to model patient immunity to an experimental autologous dendritic cell (derived from patients) – allogeneic canine mammary tumor vaccine. After obtaining my DVM, I went to Johns Hopkins to pursue a residency in veterinary anatomic pathology and postdoctoral research in cancer immunology and translational medicine. While at Johns Hopkins in the departments of Molecular and Comparative Pathobiology and Oncology, I completed my residency training in veterinary anatomic pathology and obtained additional training in tumor immunology and translational medicine with Dr. Leisha Emens (M.D., Ph.D.) My postdoctoral research in Dr. Emens lab focused on evaluating the therapeutic potential of the STING agonist ADU-S100 in combination with immune checkpoint blockade. After completion of my postdoctoral fellowship, I was appointed as a faculty member in the departments of Microbiology and Animal Resources Program where I currently serve as both an investigator in Microbiology and veterinary anatomic pathologist for ARP.

Society Memberships
Organization Name Position Held Org Link
American Association for Cancer Research  Associate Member  http://www.aacr.org/Pages/Home.aspx 
American College of Veterinary Pathologists  Diplomate   http://www.acvp.org/ 
 

Research/Clinical Interest
Title
Description
PATHOLOGY SUPPORT: As a comparative pathologist for ARP, I also contribute significant service-specific component to UAB in the form of pathology support to research projects bridging a wide span of research areas, including cancer, autoimmunity, mucosal and transplant immunology. These collaborations involve rodent, porcine, primate models and canine cancer patients. The goal of these collaborations is to provide comparative pathology support to investigators in their respective projects. As a veterinary anatomic pathologist for UAB ARP, I contribute the UAB animal health mission of ARP by provision of diagnostic necropsies and histopathology to support the mission to maintain health and wellbeing of the animal research colonies here at UAB. INDEPENDENT RESEARCH INTERESTS: Infiltrating pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States and it is one of the most fatal human malignancies, with an overall 5-year survival rate of 11%. Both response to standard-of-care and immune checkpoint therapies is poor requiring alternate strategies to induce patient-specific immune responses. In pancreatic cancer pro-tumorigenic macrophage, T regulatory cells, myeloid-derived suppressor cells, and tumor-associated fibroblasts are present within the tumor beginning at early pre-invasive stages of pancreatic cancer development. These cellular subsets inhibit T cell activation and CD8+ T cell recruitment into the tumor. Additional studies have implicated tumor infiltrating B cells as a tumor-promoting subset required for epithelial carcinoma progression enhancing tumor cell survival and contributing to chronic inflammatory cues critical to tumor progression. Additionally tumor progression, immunosuppression, and response to therapy are linked to constitutive oncogenic KRAS signaling. Approximately 94% of patient tumors have codon specific mutations in KRAS, in particular >90% mutations involved codon 12 (Glycine to Aspartic acid, Arginine or Valine). The focus of my independent research falls into 2 categories: (i) Basic tumor biologic study investigating the role of antibody responses in the PDAC TiME and their role in tumor progression and tumor immunity and (ii) translational immune oncology investigating the role of targeted oncogenic KRAS inhibitors on innate and adaptive immunity in the PDAC TiME. PROJECT 1 (Basic Tumor Immunology): Our preliminary findings in mouse models of Kras-driven pancreatic cancer indicate that antibodies appear to play an important role in modulation of tumor immune responses and deposition of extracellular matrix (can constitute up to 70% of PDAC TME). The major goal of my current research focus in this area is to determine requirements for antibody-driven, pancreatic tumor-specific immunity using mouse models that closely recapitulate disease progression observed in patients. Findings from these studies will expand our understanding of the role of antibody production within the TME on tumor progression. PROJECT 2 (Translational Immunotherapy): Our preliminary findings evaluating the immune modulatory efficacy of a pan-RAS inhibitor in PDAC highlight a role for inhibition of oncogenic KRAS (G12D) signaling in modulation of innate and adaptive immune responses in the PDAC TiME. The goal of these research studies are to understand mechanisms in which targeted inhibitors to oncogenic KRAS modulate tumor immunity in pancreatic cancer and to determine if inhibition of oncogenic KRAS sensitizes patients to previously, non-efficacious immune checkpoint blockade. Furthermore, we intend to evaluate the impact of obesity on the efficacy of pan- and mutation specific KRAS inhibitors in lean and obese patients.

Selected Publications 
Foote JB, Kok M, Leatherman JM, Armstrong TD, Marcinkowski BC, Ojalvo LS, Kanne DB, Jaffee EM, Dubensky TW, Emens LA. A STING Agonist Given with OX40 Receptor and PD-L1 Modulators Primes Immunity and Reduces Tumor Growth in Tolerized Mice. Cancer Immunol Res. 2017 May 8   28483787 
Sunay ME, Foote JB, Leatherman JM, Edwards JE, Armstrong TD, Nirschl CJ, Hicks J, and Emens LA. Sorafenib has T cell-dependent activity and accelerates tumor clearance in vaccinated mice. Int Immunopharmacol. 2017 May;46:112-123.  28282575 
Cimino-Mathews A, Foote JB, Emens LA. Immune targeting in breast cancer. Oncology (Williston Park). 2015 May;29(5):375-85.  25979549 
Foote JB, Kabir FM, Graff EC, Cattley RC, DeInnocentes P, Smith BF, Bird Canine PBL-SCID mice: A model of the canine immune system. Vet Immunol Immunopathol. 2014 Feb 15;157(3-4):131-41.   24368085 
Foote JB, Mahmoud T, Vale AM, Kearney JF. 2011. Generation of two distinct plasma cell populations with different degrees of cell turnover in response to the bacterial polysaccharide  13 dextran. Journal of Immunology. 2012 Jan 1;188(1):57-67.  22116821 
Foote JB and Kearney JF. 2009. Generation of B cell memory to the polysaccharide antigen alpha 13-dextran. Journal of Immunology. Nov 15;183(10):6359-68.   19841173 
 

Keywords
Comparative Pathology, Pancreatic cancer, B cells, Antibody, Immunotherapy, KRAS