Lilia Y Kucheryavykh, PhD
Associate Professor, Dept. of Biochemistry, Universidad Central del Caribe
PROJECT TITLE:
MYELOID CELL CIRCUIT IN PRIMARY AND RECURRENT GLIOBLASTOMA TUMORS
I conduct Brain Tumor Research Program at the Universidad Central del Caribe (UCC). In the framework of the program, I am involved in research mentoring of early career investigators, graduate and undergraduate students. Within the program, I conduct few active research projects based on broad interdisciplinary collaboration in areas of physics and chemistry:
Investigation of the mechanisms of interaction of brain tumor glioma cells with infiltrating microglia/macrophages.Microglia infiltrate most gliomas and have been demonstrated to promote tumor growth, invasion, and treatment resistance. We have identified Pyk2 and FAK as a new intracellular signaling elements mediating interactions between microglia and glioma cells (Rolón-Reyes et al., 2015; Nunez et al., 2021) and involved in fast tumor relapse after surgery resection. The current studies are directed at the development of combinatorial therapies utilizing dual Pyk2/FAK inhibitors together with chemotherapeutic compounds to target the microglial component on tumor progression and recurrence after surgery resection. Glioma mouse models and resected primary human glioblastoma tissues are used. Research is supported by NIH SC1 funding mechanism and is conducted in collaboration with the University of Puerto Rico Medical Center and HIMA San Pablo Hospital, Caguas, based on the IRB approval.
Investigation of mechanisms of brain tumor development in HIV-positive patients. HIV infection creates tumor microenvironment with increased load of viral proteins, as gp120. We demonstrated that gp120, mostly originated from infected microglia and astrocytes, leads to metabolic changes in glioma tumor cells resulting in increased tumor growth and chemotherapeutic resistance (López et al., 2017; Valentín-Guillama et al, 2018). The mechanisms of gp120-dependant metabolic changes in glioma tumors are currently under investigation in our laboratory. HIV mouse models and primary human glioma cell lines are used.
Platelet-generated amyloid beta peptides are accumulated in brain during blood vessels thrombosis and brain cancer. We demonstrated a massive release of beta-amyloid (Aβ) inside clotted blood vessels in brain. Thrombosis induced in the entorhinal cortex of mice causes an accumulation of Aβ peptide outside and around the blood vessels in brain parenchyma. These findings suggest an additional source of Aβ in brain that may arise when constant thrombosis events occur.
The Rac inhibitors HV-107 and HV-118 as potential therapeutics for metastatic breast cancer. Rac inhibitors are tested as a targeted therapy for breast cancer treatment in vivo and in vitro. Studies are conducted in collaboration with Dr. S. Dharmawardhane, Department of Biochemistry, UPR, and Dr. Cornelis Vlaar, Department of Pharmaceutical Sciences, School of Pharmacy, UPR.