Research in Frolov lab is focused on how the major tumor suppressor pathway, the Retinoblastoma (RB) pathway, regulates cell proliferation, differentiation and metabolism and why inactivation of RB pathway such a prominent event in human cancer. To address these questions we employ biochemical, genetic, genome-wide and single cell genomic approaches primarily using a simpler Drosophila model system. Our lab is fully adept in computational analysis of genome-wide data and therefore students acquire necessary bioinformatic skills. There are several rotation projects available that are broadly outlined below. Single Cell Genomics Single cell genomics (scRNA-seq and scATAC-seq) revolutionized the field in addressing many challenging questions in cancer biology. Among them are tumor heterogeneity, metastatic potential of tumors, basis of drug resistance acquired by tumors during treatment and many others. In our lab, we are using state of the art single cell measurements such as Drop-seq and 10X Genomics to understand how mutations in RB pathway affect different cell types (for example: Ariss et al 2018 Nature communications that featured in UIC Press Release, November 28, 2018). We are active participants of The Fly Cell Atlas, a collaborative project that brings together researchers building comprehensive cell atlases during different developmental stages and disease models. RB Pathway and Cellular Metabolism A major focus of our recent work is how RB pathway controls cellular metabolism. We discovered that RB pathway regulates mitochondrial function in Drosophila (Developmental Cell 2013). We used the results generated in flies to guide our studies in mammalian cells and showed that mammalian RB pathway operates in a highly analogous manner. Given that muscles are highly sensitive to mitochondrial dysfunction, we followed up on this initial observation and examined the role of E2F and pRB in developing skeletal muscles (Zappia and Frolov, 2016, Nature Communications and Zappia et al, 2019, Cell Reports, this work is featured in UIC Cancer Center Newsletter, February 19, 2019). Our next goal is to decipher the contribution of the RB pathway in regulation of metabolic genes and importance of its regulation during muscle development.
– Single cell RNA-sequencing identiﬁes a metabolic aspect of apoptosis in Rbf mutant.
– Rbf Activates the Myogenic Transcriptional Program to Promote Skeletal Muscle Differentiation.