Joseph Heitman is interested in the signaling pathways that regulate the differentiation and virulence of microorganisms and in the signaling pathways that are inhibited by natural product toxins, including the immunosuppressants cyclosporin, FK506, and rapamycin. Our research focuses on how cells sense their environment and communicate with other cells via signal transduction cascades. Our studies address the mechanisms of action and targets of antifungal drugs that also suppress the immune system and the mechanisms by which yeast and fungal cells sense and respond to the environment and the host. Our findings reveal elements of signal transduction cascades conserved from yeast and fungi to humans over the billion years of evolution separating us from a common ancestor.
All organisms sense and respond to nutrients.
Many signal transduction pathways in microorganisms are devoted to sensing the availability of nutrients, including sugars, amino acids, and nitrogen sources. We study how cells sense nutrients during filamentous differentiation in S. cerevisiae and mating and virulence in C. neoformans . In response to adverse nutritional conditions, diploid yeast cells differentiate, undergoing a dimorphic transition called pseudohyphal growth in which the cells elongate and then grow in filaments that extend away from the colony and into the growth medium to forage for nutrients. We have delineated a signal transduction cascade that regulates filamentous growth. In contrast, the related PKA catalytic subunits Tpk1 and Tpk3 play a negative role in regulating filamentation, either by feedback inhibition of cAMP production or by competing with Tpk2 for downstream targets.