|
|
 |
| |
|
Sufi M Thomas
Assistant Professor
PhD
200 Lothrop St.
W915 BST
Pittsburgh, PA 15213
Phone: 412 383 5403
Email: thomsm@upmc.edu
Fax: 412 383 5409
|
| |
| Research Interests |
Despite improvements in conventional therapies, head and neck squamous cell carcinoma (HNSCC) continues to be a major challenge with poor 5-year survival rates caused primarily due to local invasion and metastasis. There are no therapies that target HNSCC invasion or can prevent metastasis. Understanding of the molecular mechanisms responsible for the highly invasive and metastatic nature of HNSCC will facilitate the development of strategies to curtail invasion and metastasis in newly diagnosed early stage patients or in patients who undergo surgery with curative intent. We observed that tumor associated fibroblasts (TAFs) induce HNSCC invasion and metastasis. My laboratory is focused up on identifying the mechanisms whereby TAFs facilitate HNSCC progression. TAFs express receptors that are activated in the presence of HNSCC conditioned media. These result in an increase in fibroblast proliferation. The signaling mechanisms behind these effects are being examined using techniques including immunoblotting and immunofluorescence. Factors secreted by the fibroblasts induce HNSCC invasion. One such factor is the hepatocyte growth factor. Identification of molecules that are involved in tumor-stromal fibroblast cross-talk are critical in developing strategies to curtail TAF induces tumor progression.
One of the impediments to cancer therapy is the lack of specific inhibitors to molecular targets. Gene therapy with antisense oligonucleotides can be used to specifically target molecules that are important for tumor growth and progression. Dr. Thomas has developed a therapeutic approach where genes critical for tumor survival are specifically attenuated with systemically delivered antisense oligonucleotides. In collaboration with a chemist Dr. Danith Ly from CMU, antisense oligonucleotides targeting the epidermal growth factor receptor (EGFR) with a modified peptide nucleic acid backbone amenable to systemic delivery has been developed. Since PNA oligomers have poor cellular uptake, positively charged guanidinium groups were incorporated in the PNA backbone. The resulting EGFR antisense guanidinium peptide nucleic acid (EGFRAS GPNA) oligomers demonstrated specific antitumor effects that are comparable to EGFR inhibitors erlotinib and cetuximab. Identification of other targets with therapeutic potential that lack specific inhibitors is currently underway. This method of systemic delivered antisense oligonucleotides holds immense potential for antisense gene therapy applications.
Research Support:
07/01/11 – 06/30/13 Competitive Medical Research Fund,
Clinical and Translational Science Institute, University of Pittsburgh Medical Center
The role of tumor-associated fibroblasts in head and neck cancer progression
The major goal of this project is to determine the signaling molecules involved in tumor stromal cross-talk.
Role: Principal Investigator
7/1/10 – 6/30/13 Career development Award, NCI
Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer
Targeting EGFR in head and neck cancer with EGFR antisense peptide nucleic acid molecules
The major goal of this project is to develop a systemically delivered antisense approach for head and neck cancer.
Role: Principal Investigator
08/01/08 – 05/31/13 RO1 CA129829 Dr. Jian Yu (PI) NIH/NCI
Role of PUMA in the EGFR targeted therapy in HNSCC
The goal is to study the mechanism and significance of PUMA induction in the therapeutic responses to EGFR-targeting agents in Head and Neck cancer.
Role: Co-Investigator
6/15/10 – 4/30/15 R01 CA137260 Dr. Dan Johnson (PI), NIH/NCI
Molecular Targeting Strategies in HNSCC
These studies will investigate novel mechanisms that regulate HNSCC cell death following treatment with agents targeting the proteasome or anti-apoptotic Bcl-2 family members. Additionally, we will examine the in vivo efficacies and mechanisms of these agents against HNSCC tumors when used alone, or in combination, seeking to exploit pathways that confer sensitivity to these agents. Our results will provide the basis for new treatment strategies for this disease.
Role: Co-Investigator
|
| |
| Publications |
1. Mathew M, Thomas SM. In Li X (ed): Squamous Cell Carcinoma. The Cellular Microenvironment of Head and Neck Squamous Cell Carcinoma, ISBN 978-953-307-864-9. In Tech, 163-174, 2012.
2. Nozawa H, Howell G, Suzuki S, Zhang Q, Qi Y, Klein-Seetharaman JK, Wells A, Grandis JR, Thomas SM*. Combined inhibition of PLC•-1 and c-Src abrogates epidermal growth factor receptor mediated head and neck squamous cell carcinoma invasion, Clinical Cancer Research, 2008,14:4336-43. PMCID: PMC3358699.
3. Thomas SM, Coppelli FM, Drenning SD, Song JI, Kassis J, Gooding WE, Wells A, Grandis JR. Epidermal growth factor receptor-stimulated activation of PLC•-1 mediates invasion of head and neck squamous cell carcinoma in vitro. Cancer Research, 2003 (63): 5629-5635. PMID: 14500405.
4. Sahu B, Chenna V, Lathrop KL, Thomas SM, Zon G, Livak KJ, Ly DH. Synthesis of conformationally preorganized and cell-permeable guanidine-based-peptide nucleic acids (GPNA), Journal of Organic Chemistry, 2009, 74:1509-1516. PMCID: PMC2650244.
5. Lai SY, Koppikar P, Thomas SM, Childs EE, Egloff AM, Seethala RR, Branstetter BF, Gooding WE, Siwak DR, Muthukrishnan A, Mountz JM, Lui VWY, Shin DM, Agarwal SS, Johnson R, Couture LA, Myers E, Johnson JT, Mills G, Argiris A, Grandis JR. Intratumoral EGFR antisense DNA therapy in head and neck cancer: First Human application and potential antitumor mechanisms. Journal of Clinical Oncology, 2009, 10;27(8):1235-42. PMCID: PMC2667824.
|
| |
| Education |
2000-2003 Research Associate at the University of Pittsburgh
2000 Ph.D in Applied Biology from Mumbai University, India
1994 M.Sc in Life Sciences (Biotechnology) from Mumbai University, India
1992 B.Sc in Life sciences from Sophia college, Bombay University, India
|
| |
| Grants |
2007-2008 Developmental research Project,
Specialized Program of Research Excellence (SPORE) in Lung Cancer
Targeting EGFR in lung cancer with EGFR guanidinium antisense peptide nucleic acids Role: Principle Investigator
2006-2008 Research grant from Applied Biosystems Incorporated Dr. Danith Ly (PI)
Development of a Second Generation Cell-Permeable GPNA
Role: Co-Investigator
2006-2007 Developmental research Project,
Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer
Targeting EGFR in head and neck cancer with EGFR antisense peptide nucleic acid molecules
Role: Principle Investigator
2006-2011 1 R01 CA115902-01 Dr. Robert Ferris (PI), NIH/NCI
Chemokine Signals in Head and Neck Cancer Progression
Role: Co-Investigator
2004-2009 1 U01 CA 101244-01 Dr. Dong Shin (PI), NIH/NCI
Chemoprevention of HNC with Erlotinib & Celecoxib
Role: Co-Investigator
2005-2006 Research grant from Imclone Systems
Combined inhibition of EGFR and GPCR autocrine signaling in head and neck squamous cell carcinoma
Role: Principal Investigator
2005-2006 Grant from Eli-Lilly Incorporated
|
| |
|
