Katherine Block, PhD

Sr. Development Scientist, Beckman Coulter
PhD (2010)
Advisor: Dr. Myron Jacobson

My dissertation research involved two independent projects in the development of novel cancer therapeutics: (1) agents targeting tumor hypoxia and (2) agents targeting DNA repair. Most solid tumors typically exhibit hypoxia, which is the state of reduced oxygen levels. Hypoxia activates the HIF-1? (hypoxia inducible factor) signaling pathway, which represents a major amplification point in cancer progression. HIF-1? regulates transcription of key genes controlling angiogenesis, glucose metabolism, and metastasis, all of which are highly over-expressed in cancer.
Our lab synthesized a new class of transcriptional inhibitors called ETPs (epidithiodiketopiperazines) designed to block a protein-protein interaction between HIF-1? and its required coactivator, p300/CBP. My work focused on determining the efficacy and mechanism of action of these transcriptional inhibitors, and was featured on the cover of the Journal of the American Chemical Society Dec. 23rd, 2009 issue. Understanding the molecular mechanisms involved in DNA repair is critical to developing improved, safer cancer treatments. When DNA damage occurs, polymers of ADP-ribose (PAR) are formed to assess the level of damage and to coordinate a cellular response. Poly(ADP-ribose) polymerase (PARP) synthesizes these polymers, while poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme capable of degrading PAR. PARP is a well-known and well-validated target in chemotherapeutics, however, the role of PARG is relatively unexplored. My work on this project involved the evaluation of PARG as a new therapeutic target in cancer treatment.
I am currently a Research Specialist doing pancreatic cancer research with Dr. Amanda Baker My work involves evaluating the role of Pim-1 kinase signaling in pancreatic cancer. Most pancreatic tumors have a strong inflammatory component resulting from the surrounding stroma. These studies examine the relationship between tumor and stromal tissue with regard to survival signaling and cancer progression.
Pharmaceutical Sciences
Drug Discovery and Development
Dissertation Title: 
“Design of Novel Cancer Therapeutics through the Validation of PARG as a Therapeutic Target and the Evaluation of Small Molecule Inhibitors of Hypoxia-Induced Transcription”
1.  Katherine M. Block  and Myron K. Jacobson. Validation Studies of PARG as a Therapeutic Target. Exp. Cell Res. (2010), in preparation.
2.  Katherine M. Block, Hui Wang, Lajos Z. Szabo, Nathan W. Polaske, Laura K. Henchey, Ramin Dubey, Swati Kushal, Csaba F. Laszlo, Joshua Makhoul, Zuohe Song, Emmanuelle J. Meuillet, and Bogdan Z. Olenyuk. Direct Inhibition of Hypoxia-Inducible Complex with Designed Dimeric Epidithiodiketopiperazine. J. Am. Chem. Soc. (2009), 131, 17995-18190.
3. Po-Chang Chiang, Chiang Ching-Su, Katherine Block, and Denise Pretzer. Medium throughput pKa determinations of drugs and chemicals by using a HPLC equipped with DAD as a flow injection apparatus. J. Liq. Chromatogr. Relat. Technol. (2005) 28, 3035-3043.
Alumna or Alumnus: 
Alumni Title/Position/Employer: 
Clinical Biomarker and CDx Strategy Lead, AbbVie, Companion Diagnostics Center of Excellence
Career Type: