Trainee Spotlight: Galina Semenova
I grew up in Tambov, Russia, a mid-sized city 300 miles south-east of Moscow, in a rather artistic family where I dreamt of becoming an actress. As a teenager, I was passionate about ballroom dancing, piano and literature and, at the same time, began to express intense interest in natural sciences. I attended a specialized high school with advanced classes in chemistry and biology, and regularly participated in academic high school competitions. Torn between art and science I wondered if I would ever be able to find a profession that would satisfy my scientific curiosity as well as my need for creative practice. Now, with the perspective of a few years, I can say that this is exactly how I see the profession of academic researcher—I couldn’t be happier with the path I chose!
I studied for my degree of Doctor Biochemist at the Russian National Research Medical University (RNRMU), Moscow, Russia. My training included courses in basic sciences and a number of clinical courses, allowing me to continue my education in either medicine or biology. For my last year of training, I joined the Department of Molecular Biology and Medical Biotechnology at RNRMU and enrolled in Fox Chase-RNRMU Sister Institute Program. I was extremely fortunate to join Dr. Jonathan Chernoff’s lab at Fox Chase Cancer Center where I worked on induced pluripotent stem cell models of Schwann cell differentiation in order to study tumors associated with Neurofibromatosis type I. After a year in Chernoff’s lab, and subsequent graduation from RNRMU, I have now returned to Fox Chase as a fully committed basic scientist. My current work is focused on the role of p21-activated kinases in malignant peripheral nerve sheath tumor (MPNST) biology and includes investigation of molecular mechanisms underlying tumor development and progression as well as experimental therapies. My immediate goal is to complete my PhD training and pursue a career in biological research as a postdoctoral associate.
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating sarcomas for which no effective medical therapies exist. Over 50% of MPSNTs are associated with mutations in NF1 tumor suppressor gene, resulting in activation of Ras and its effectors, including the Raf/Mek/Erk and PI3K/Akt/mTORC1 signaling cascades, as well as the WNT/ β-catenin pathway. As Group I p21-activated kinases (PAK1/2/3) have been shown to modulate Ras-driven oncogenesis, we asked if these enzymes might regulate signaling in MPNSTs. In this study, we found a strong positive correlation between the activity of PAK1/2/3 and the stage of human MPNSTs. We determined that reducing Group I Pak activity diminished MPNST cell proliferation and motility, and that these effects were not accompanied by significant blockade of the Raf/Mek/Erk pathway, but rather by reductions in Akt and β-catenin activity. Using the small molecule PAK1/2/3 inhibitor Frax1036, and the MEK1/2 inhibitor, PD0325901, we showed that the combination of these two agents synergistically inhibited MPNST cell growth in vitro and dramatically decreased local and metastatic MPNST growth in animal models. Taken together, these data provide new insights into MPNST signaling deregulation and suggest that co-targeting of PAK1/2/3 and MEK1/2 may be effective in the treatment of patients with MPNSTs.
Galina Seminova, Dina Stepanova, Cara Dubyk, Elizabeth Handorf, Sergey Deyev, Alexander Lazar and Jon Chernoff. Targeting group I p21-activated kinases to control malignant peripheral nerve sheath tumor growth and metastasis. Oncogene. 2017 May 22; 1-11.