Sandeep Vellanki, PhD
Tolerance provides an epistatic background for the emergence of antifungal resistance.
ΔingA biofilms showing growth defect in host-relevant oxygen levels.
About Me
Sandeep holds a master’s and Ph.D. in Cell and Molecular Biology from The University of Texas at San Antonio. His doctoral research in Dr. Soo Chan Lee’s lab focused on acquired resistance to calcineurin inhibitors in Mucorales and fungal-endothelium interactions in mucormycosis and candidiasis.
Sandeep was awarded a postdoctoral fellowship from the Cystic Fibrosis Foundation to identify epigenetic mechanisms promoting Aspergillus fumigatus adaptation to CF-relevant conditions and stress response in the Cramer lab. During his fellowship, he investigated the role of Inhibitor of Growth (ING) family proteins in low-oxygen adaptation, disease progression, and drug susceptibility. Analysis of longitudinal isolates from both CF and CGD patients revealed the presence of allelic variants and gain-of-stop mutations in the ingB gene. The loss of ingB resulted in tolerance to azoles - the frontline antifungals used to treat aspergillosis. Subsequent exposure to high concentrations of azoles resulted in a frameshift mutation in a proteasome maturation factor, UmpA, leading to acquired resistance. Since these resistant mutations emerged only in the tolerant background, whereas the susceptible strain failed to acquire them, Sandeep’s work demonstrates that tolerance paves the way for the emergence of antifungal resistance.
Building on a genetic screen performed in N. crassa to identify novel regulators of low-oxygen adaptation, Sandeep found that the loss of ingA in A. fumigatus results in reduced fitness under host-relevant oxygen levels and attenuated virulence in vivo. Given that IngA is a putative member of the Rpd3L complex, he is currently testing whether this loss impairs the ability of A. fumigatus to “turn off” specific genes during low oxygen conditions - stay tuned for more on that! Furthermore, because low-oxygen gradients also develop during biofilm formation, Sandeep is investigating biofilm heterogeneity at the single-cell level.
When not having fun with fungi, he enjoys a mix of gym, outdoors, salsa, and listening to his cat’s complaints.
View Sandeep’s full publication list on PubMed.