GUDIPATI LAB
Our laboratory studies the functions of evolutionarily conserved and clinically relevant DPPIV family proteases and RNA binding proteins. Through focused research projects, we aim to define the interplay between these proteases and RNA binding proteins, and to elucidate the regulatory mechanisms by which they control gene expression. Ultimately, we explore how these pathways can be leveraged to address specific neurological disorders
Development of Specific and potent inhibitors of C. elegans DPF-3
Aditya Trivedi aims to develop selective inhibitors of the Caenorhabditis elegans protease DPF-3, a key regulator of small RNA-mediated silencing, while minimizing inhibition of human DPPIV family proteases. He uses a dual-assay screening strategy utilizing both biochemical and organismal approaches. First, candidate compounds are screened for enzyme inhibition using recombinant DPF-3 and a fluorogenic substrate. Second, the selected compounds are tested in vivo using a C. elegans strain carrying a fluorescent reporter (Pzc15.3::ZC15.3-Wrm Scarlet::ZC15.3 3’UTR), which enables direct visualization of DPF-3 inhibition via red fluorescence triggered by de-silencing of the ZC15.3 transposon. This whole-organism biosensor provides a rapid and quantitative readout of target engagement.
Repeat expansion disorders and the role of DPPIV proteases
Damini Saha’s research is geared towards the applicability of DPPIV family proteases to address repeat expansion disorders that are a class of genetic diseases caused by abnormal expansion of short DNA repeat sequences, often located in non-coding regions of the genome. These expansions give rise to toxic RNA species that form stable secondary structures and sequester essential RNA-binding proteins, disrupting post-transcriptional gene regulation. In parallel, repeat-associated non-AUG (RAN) translation produces aggregation-prone proteins that interfere with proteostasis, nucleocytoplasmic transport, and stress response pathways. Together, these mechanisms trigger DNA damage, transcriptional dysregulation, and progressive neuronal dysfunction, ultimately leading to neurodegeneration. We are exploring how the DPPIV proteases can be harnessed to address the protein aggregates that cause specific neurodegenerative diseases.
Regulation of Argonaute ALG‑1 Activity by the protease, DPF-3
Afzal Amanullah’s PhD research examines how microRNA (miRNA) pathway activity is regulated to ensure robust gene silencing during development. His work focuses on the regulation of the miRNA Argonaute ALG-1 by the dipeptidyl peptidase DPF-3. Through genetic and phenotypic analyses, this research investigates how modulation of ALG-1 function influences miRNA-mediated gene regulation and developmental stability. By defining regulatory interactions within the miRNA machinery, this work aims to elucidate mechanisms that fine-tune small RNA-dependent gene expression regulation
Gene expression regulation by RNA binding proteins - PUF proteins
Ilkin Aygun’s project examines the role of RNA binding proteins in gene expression regulation, particularly in germ cells. Germline development relies heavily on post-transcriptional gene regulation, as transcriptional activity in germ cells is spatially and temporally restricted. RNA binding proteins therefore play a central role in controlling germline stem cell maintenance, differentiation, and fertility. In this study, she investigates the molecular function of the evolutionarily conserved Pumilio family RNA binding protein PUF-9 in Caenorhabditis elegans, a member that has remained largely uncharacterized despite extensive knowledge of other PUF proteins. Preliminary phenotypic analyses of puf-9 mutant animals reveal several developmental as well as reproductive defects. To elucidate the underlying molecular mechanisms, we combine phenotypic analysis with systematic identification of PUF-9 RNA targets and interacting protein partners. By defining the post-transcriptional regulatory network governed by PUF-9, this work aims to uncover how PUF-9 modulates germline gene expression programs. Given the evolutionary conservation of PUF proteins, our findings provide insight into fundamental mechanisms of germline regulation with broader relevance across metazoans.
Discovering a New Guardian of Genome Stability
Ankit Roy’s research focuses on the mechanisms by which cells protect their genomes from transposable elements, the “jumping genes” that pose constant threats to genomic integrity. Our recent work identifies picd-1, a previously uncharacterized protein, as an essential factor in maintaining genome stability in the C. elegans germline. When picd-1 is absent, animals show progressive germline decline and sterility, particularly at elevated temperatures. This temperature-sensitive phenotype suggests that picd-1 function becomes critical under environmental stress. PICD-1 regulates components of small RNA pathways, systems that cells use to silence transposable elements and protect genome integrity across generations. The conservation of PICD-1's protein domains from nematodes to humans hints that similar mechanisms may operate across species, potentially offering insights into fertility, genome stability, and stress responses in higher organisms.