Lamia Wahba, Ph.D.
Assistant Professor
The Rockefeller University
The Wahba Lab

Dr. Wahba did her graduate work at the Carnegie Institute’s Dept of Embryology, located on the Hopkins campus. There she worked on R-loops in budding yeast under the mentorship of Douglas Koshland. For her postdoc she moved to Andy Fire’s lab at Stanford to study small RNA systems in the free-living nematode Caenorhabditis elegans. She joined Rockefeller as an assistant professor in 2023.     

The Wahba lab seeks to understand the role of nongenetic inheritance mechanisms in disease and evolutionary processes by dissecting the processes and parameters influencing it, the biological functions impacted, and their physiological relevance. Research in the lab builds on Wahba’s previous findings about the role of small RNAs and their protein partners, Argonautes, in the transgenerational maintenance of the germline’s immortal character. In most metazoans, Argonaute/sRNA systems are central to the transgenerational inheritance of gene regulation programs, but a full mechanistic understanding of initiation and inheritance determinants remains under investigation.

Using the free-living nematode C. elegans as a model system, Wahba’s work has found that some heritable sRNAs propagate through self-perpetuating amplification cycles, a strategy that allows for the indefinite spread of silencing signals across generations but risks overamplifying them. To limit the potentially dire consequences of sRNA overamplification, Wahba identified the piRNA pathway (involving a second type of Argonaute/sRNA ribonucleoprotein) as an essential negative modulator of it. In the absence of piRNAs, worms progressively lose fertility over multiple generations until they become completely sterile, the result of genes targeted by endogenous Argonautes/sRNAs succumbing to perpetual and inappropriate transgenerational silencing.

The roles Argonautes/sRNAs play in maintaining germline mortality highlight the potent nature of nongenetic inheritance, and the existence of molecular machineries dedicated to its active limitation and regulation. By delineating the mechanistic principles underlying acquisition and inheritance of nongenetic information, the Wahba lab’s ultimate hope is to address a fundamental question facing researchers across many biological fields: whether it is time to revamp the framework for inheritance to incorporate transmission of molecular factors that transcend DNA sequences.

Hosted by Colin Conine, Ph.D.