Welcome to the website for the Madhani laboratory in the Department of Biochemistry and Biophysics. We are located in Genentech Hall at the UCSF Mission Bay Campus. We are affiliated with the Tetrad graduate program, iPQB graduate program, the California Institute for Quantitative Biosciences (qb3) and the Helen Diller Family Comprehensive Cancer Center.
We study the battles within and between organisms that drive the evolution of the eukaryotic organisms:
(1) RNA-guided genome defense: the spliceosome and beyond
We are fascinated by the biology and evolution of mechanisms that distinguish cellular genes from parasitic (or “selfish”) nucleic acids. We focus on the intriguing mechanisms that recognize silence selfish DNAs them using chromatin- and small RNA-based mechanisms. We use powerful yeast model systems (S. pombe and C. neoformans) to develop a general mechanistic understanding of the principles of selfish element recognition and silencing. We believe that such knowledge will illuminate the evolution of gene expression in eukaryotes, which differs dramatically from the analogous mechanisms of bacteria. Our recent studies have revealed unexpected role for noncoding RNAs including introns and the spliceosome in genome defense, which may help to explain the persistence of introns in eukaryotes.
(2) Host-pathogen interactions during fungal infection
Cryptococcus neoformans is responsible for 1 million new infections annually in highly immunocompromised individuals, most of which result in death due to meningitis. As the only human pathogenic fungus with a complete sexual cycle and haploid genetics, this budding yeast offers powerful experimental advantages for understanding the molecular basis of its success as a human pathogen. Our recent studies have elucidated a dense transcriptional networks and novel secreted effectors that control the ability of the pathogen to resist phagocytosis and cause disease.