|Institution||College of Medicine|
|Address||500 University Drive Hershey PA 17033|
Professor of Pathology, and Biochemistry and Molecular Biology
GRADUATE PROGRAM AFFILIATIONS:
Biochemistry and Molecular Biology, Cell and Molecular Biology, Integrative Biosciences, MD/PhD Degree Program
Ph.D., Michigan State University, 1976
Postdoctoral Training, University of California, San Francisco, 1977-1981
M.D., University of Miami, 1983
Anatomic Pathology Residency, University of California, San Francisco, 1983-85
Assistant Professor, Pathology, University of California, San Francisco, 1985-1987
Associate Professor, Pathology, George Washington University, 1987-1991
Associate Professor and Professor, Pathology, Hershey Medical Center, Pennsylvania State University, 1991-Present
There are 2 main areas of investigation in the Clawson laboratory.
1) Development of a chip-based sensor platform for detection of circulating tumor cells (CTCs). This work is ongoing in collaboration with the Keating (Chemistry) and Mayer (Electrical Engineering) laboratories at University Park. The approach consists of a hybridization “sandwich” using pre-selected target RNAs for a particular cancer (e.g., PCA3 for prostate cancer). Target RNAs are synthesized, optimal binding sites for antisense oligonucleotides are identified using a library selection technique, and they are tested in pair-wise fashion to optimize the sandwich binding. Nanowires (NWs) are functionalized with one of the ASOs, and 50 nm gold nanoparticles (AuNPs) are functionalized with the 2nd ASO (for mass amplification). NWs are electrofluidically deposited onto pre-determined addresses on CMOS chips, which allows for multiplexing for 10’s-100’s of different target RNAs for various cancers. CTCs are enriched from patient blood specimens using a simple porous membrane centrifugation device (OncoQuickTM), which enriches CTXs ~ 400X, and RNA is extracted. This enriched RNA is then bound to the chip-based NWs and the AuNPs. Detection of the bound complexes (target RNA:AuNPs) is currently accomplished by measuring shifts in the resonance frequency of the NWs, due to the added mass of the sandwich complexes, although direct electrical detection is now being focused on. We currently have clinical trials going on with early stage melanoma patients, as well as protocols for colon and pancreatic cancer patients; we are using conventional QPCR to measure target transcript levels for the various cancers, and will then test the samples using the chip-based platform when it is operational.
2) Role of the potential tumor suppressor HtrA1 in carcinogenesis. Our recent work has identified HtrA1 as a key control element for the epithelial-to-mesenchymal transition (EMT), as well as a control for error-prone DNA damage repair. We are currently investigating molecular mechanisms of action by which HtrA1 regulates the EMT, and how it controls ATM-mediated DNA damage pathways.
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