Assistant Professor
Texas Tech University Health Sciences Center
I was recently appointed as Assistant Professor (tenure track) in the Department of Pediatrics, TTUHSC School of Medicine. I have received extensive training in preclinical cancer therapeutics. My primary objective is to discover innovative therapies that can enhance outcomes for pediatric cancer patients. Currently, my laboratory is dedicated to uncovering unique therapeutic vulnerabilities in osteosarcomas that employ alternative lengthening of telomeres (ALT) to maintain their telomere length and achieve replicative immortality. My academic training and research experiences have equipped me with a strong foundation in molecular biology, biochemistry, genetics, and pre-clinical cancer therapeutics. My prior training was centered on elucidating telomere maintenance mechanisms in high-risk neuroblastoma (NB), specifically the ALT mechanism. Our research demonstrated that the analysis of TERT mRNA expression and C-circles (a specific DNA marker for ALT) enables precise risk stratification of high-risk NB patients, regardless of the currently employed risk factors (Koneru, B. et al., Cancer Research, 2020). Currently, we are validating our findings in collaboration with the Children’s Oncology Group (COG) using most recently completed COG phase III neuroblastoma clinical trial (ANBL0532) patient samples. In a concurrent study, we illustrated that ALT NB consistently exhibit elevated levels of activated ATM, resulting in de novo resistance to DNA-damaging agents, which can be reversed with the ATM inhibitor AZD0156 (Koneru, B. et al., Science Translational Medicine, 2021). Furthermore, we demonstrated that ATM kinase remains constitutively active in ALT cancers due to inherent telomere dysfunction, leading to hypersensitivity to p53 reactivation using the clinical-stage drug APR-246 in ALT patient-derived cell lines and xenografts from various adult and pediatric cancers (Macha SJ & Koneru B, et al., Cancer Research, 2022). My current research goals are to continue working on telomere maintenance mechanisms in childhood cancers together with a major new focus on pre-clinical therapeutic studies for ALT osteosarcoma.
