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Department of Medicine

Department of Medicine

  Division of Hematology/Oncology

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Lan G Coffman, MD, PhD

Email: coffmanl@mail.magee.edu

Phone: 412-641-2016

Contact
Office: B401 MWRI
204 Craft Avenue
Pittsurgh, PA 15213
 
Phone: 412-641-2016
Fax: 412-641-2458
E-mail: coffmanl@mail.magee.edu
Administrative Assistant:
Renee Mandell
Address: 204 Craft Avenue
402 MWRI
Pittsburgh, PA 15213
Email: mandellr2@upmc.edu
Phone: 412-641-7724
Fax: 412-641-2458
Education and Training
Education
BS, Loyola College
MD, Wake Forest University School of Medicine
PhD, Wake Forest University School of Medicine
Residency, University of Michigan
Fellowship, University of Michigan
Research Interest
My research focuses on the ovarian cancer microenvironment, understanding and targeting the cancer supporting stromal tissues which are critical to the survival, growth and spread of ovarian cancer. Specifically, I study a critical non-malignant component of the ovarian cancer microenvironment, the carcinoma-associated mesenchymal stem cell (CA-MSC). CA-MSCs are stromal progenitor cells which significantly increase tumor growth. I demonstrated that CA-MSCs form a critical BMP4:hedgehog signaling loop with ovarian cancer cells. Blocking this loop with a hedgehog inhibitor prevents CA-MSC mediated tumor growth, enhancement of cancer stem cell-like cells, and chemotherapy resistance. Indeed, the combination of a hedgehog inhibitor and cisplatin not only decreased growth in naïve tumors but led to regression of well established, chemotherapy resistant tumors in a mouse model. This work provides important information regarding tumor:stromal signaling within the ovarian cancer microenvironment, describes a mechanism for the pro-tumorigenic function of CA-MSCs and potentially presents a novel therapeutic approach.
I am also investigating the role of the tumor microenvironment in ovarian cancer metastasis. New evidence demonstrates high grade serous ovarian cancer, the most common and deadly form of ovarian cancer, likely arises in the fallopian tube and the ovary is a critical initial site of metastasis. I developed three novel mouse models of ovarian cancer metastasis which demonstrate ovarian cancer is capable of hematogenous spread with a unique tropism for the ovary. Further, initial metastasis to the ovary appears to be critical for the development of intra-abdominal metastasis implicating unique aspects of the ovary microenvironment in propagating metastasis.
Clinical Interest
My clinical focus is on the treatment of gynecologic malignancies. As a medical oncologist, I work in collaboration with our Gynecologic oncologists to provide non-surgical care and perform clinical trials to develop novel therapies for women with gynecologic cancer.
Publications
Selected Publications:
Coffman LG, Brown JC, Johnson DA, Parthasarathy N, D'Agostino RB Jr, Lively MO, Hua X, Tilley SL, Muller-Esterl W, Willingham MC, Torti FM, Torti SV. Cleavage of high-molecular-weight kininogen by elastase and tryptase is inhibited by ferritin. Am J Physiol Lung Cell Mol Physiol. 2008; 294(3): 505-515.
Coffman LG, Parsonage D, D'Agostino R Jr, Torti FM, Torti SV. Regulatory effects of ferritin on angiogenesis. Proc Natl Acad Sci U S A. 2009; 106(2): 570-575.
Knovich MA, Storey JA, Coffman LG, Torti SV, Torti FM. Ferritin for the clinician. Blood Rev. 2009; 23(3): 95-104.
Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: Past, present and future. Biochim Biophys Acta. 2010; 1800(8): 760-769.
Miller LD, Coffman LG, Chou JW, Black MA, Bergh J, D'Agostino R Jr, Torti SV, Torti SV. An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res. 2011; 71(21): 6728-6738.
Coffman L, Mooney C, Lim J, Bai S, Silva I, Gong Y, Yang K, Buckanovich RJ. Endothelin receptor-A is required for the recruitment of antitumor T cells and modulates chemotherapy induction of cancer stem cells. Cancer Biol Ther. 2013; 14(2): 184-192.
Choi YJ, Ingram PN, Yang K, Coffman L, Iyengar M, Bai S, Thomas DG, Yoon E, Buckanovich RJ. Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2. Proc Natl Acad Sci U S A. 2015; 112(50): E6882-E6888.
Coffman LG, Burgos-Ojeda D, Wu R, Cho K, Bai S, Buckanovich RJ. New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination. Transl Res. 2016; 175: 62-102.
Coffman LG, Choi YJ, McLean K, Allen BL, di Magliano MP, Buckanovich RJ. Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop. Oncotarget. 2016; 7(6): 6916-6932.