August 1, 2019

Tom Kelly, Ph.D.

Associate Professor
Department of Pathology
UAMS College of Medicine

Research Interest Statement

I work with Steve Post, Ph.D., on the role of tumor-associated macrophages and scavenger receptor-A (SR-A) in promoting the rapid formation and outgrowth of tumors that we observe in the in vivo mammary tumor virus-polyoma middle T (MMTV-PyMT) model of breast cancer.

We think that SR-A activates signaling pathways in macrophages that result in production and elaboration of angiogenic cytokines and proteases. The increased angiogenesis that results promotes rapid growth of tumors that form spontaneously in this model. Our published work shows that proteolytic cleavage of collagen converts it to a good substrate for adhesion mediated by SR-A expressed by TAMs.

SR-A mediated adhesion of macrophages to collagen apparently leads to rapid tumor development and angiogenic cytokine production. Indeed, our unpublished results with in vivo models indicate that mammary tumors form more slowly in SR-A null hosts as compared to SR-A positive hosts. We have established a co-culture system in our laboratories to investigate cytokine, MMP and angiogenic factor production by wild type and SR-A null macrophages in response to tumor cells.

I am active in the Arkansas Idea Networks of Biomedical Research Excellence (AR-INBRE) led by Larry Cornett, Ph.D. I am currently preparing, with Richard Nicholas, M.D., an NIH NCI R25 grant called Arkansas-Partners in Cancer Research for Underserved and Disparities (AR-PROUD) to provide hands-on research experiences for medical students.

Dr. Kelly’s Grants

NIH\NCI

Galanzha, Ekaterina: PI

Kelly, Thomas: Co-Investigator

LYMPH LIQUID BIOPSY IN CANCER

9-11-2018 to 8-31-2020

$130,500*

 

Arkansas Breast Cancer Research Program

Post, Steven: PI

Kelly, Thomas: Co-Investigator

Role of SR-A Binding to Tumor-Associated Glycans in Breast Cancer

Project duration 2/1/2019-1/31/2020

$233,328*

*cancer-related annual direct costs

Dr. Kelly’s UAMS Collaborators

Steve Post, Ph.D., Department of Pathology

Matt Quick, M.D., Department of Pathology

Behjatolah Karbassi, Ph.D., Department of Pathology

Larry Cornett, Ph.D., Department of Physiology & Biophysics

Jerry Ware, Ph.D., Department of Physiology & Biophysics

Richard Nicholas, M.D., Department of Orthopaedics

Bobby Boyanton, M.D., Department of Pathology

Ekaterina Galanzha, Ph.D., Department of Otolaryngology – Head and Neck Surgery

Vladimir Zharov, Ph.D., Department of Otolaryngology – Head and Neck Surgery

Alan Tackett, Ph.D., Department of Biochemistry and Molecular Biology

Dr. Kelly’s External Collaborators

Guolei Zhou, Ph.D., Arkansas State University

Opportunities for Collaboration

The current R25 proposal is a great way to collaborate with me. I am looking for faculty members who want to host and mentor medical students in their research setting, be it a laboratory, a clinic or community-based research site. Otherwise, I have expertise in animal models of breast cancer, as well as cell and molecular biology techniques.

You May Not Know That …

I love to fish. I often catch largemouth bass and white bass at Lake Maumelle. I enjoy traveling with my wife. We plan to visit the Galapagos next spring.

Recent Cancer-Related Publications

Wu H, Hasan R, Zhang H, Gray J, Williams D, Miller M, Allen F, Lee V, Kelly T, Zhou GL. Phosphorylation Regulates CAP1 (Cyclase-Associated Protein 1) Functions in the Motility and Invasion of Pancreatic Cancer Cells. Sci Rep. 2019 Mar 20;9(1):4925. PubMed PMID: 30894654; PubMed Central PMCID: PMC6426867.

Holthoff ER, Byrum SD, Mackintosh SG, Kelly T, Tackett AJ, Quick CM, Post SR. Vulvar squamous cell carcinoma aggressiveness is associated with differential expression of collagen and STAT1. Clin Proteomics. 2017;14:40. PubMed PMID: 29225558; PubMed Central PMCID: PMC5717999.

Holthoff ER, Spencer H, Kelly T, Post SR, Quick CM. Pathologic features of aggressive vulvar carcinoma are associated with epithelial-mesenchymal transition. Hum Pathol. 2016 Oct;56:22-30. PubMed PMID: 27327194; PubMed Central PMCID: PMC5021565.

Jeffus SK, Gehlot A, Holthoff E, Stone R, Spencer H, Kelly T, Post SR, Quick CM. A fibromyxoid stromal response is associated with an infiltrative tumor morphology, perineural invasion, and lymph node metastasis in squamous cell carcinoma of the vulva. Am J Surg Pathol. 2015 Sep;39(9):1226-33. PubMed PMID: 26274029; PubMed Central PMCID: PMC4538995.

Holthoff ER, Jeffus SK, Gehlot A, Stone R, Erickson SW, Kelly T, Quick CM, Post SR. Perineural Invasion Is an Independent Pathologic Indicator of Recurrence in Vulvar Squamous Cell Carcinoma. Am J Surg Pathol. 2015 Aug;39(8):1070-4. PubMed PMID: 25786085; PubMed Central PMCID: PMC4503485.