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Environmental Factor, November 2012

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Hardworking postdoc receives prestigious Pathway to Independence Award

By John House

Ramendra Saha, Ph.D., and Serena Dudek, Ph.D.

Saha, left, earned his Ph.D. from the Nebraska Medical Center where he studied neurodegeneration. He considers it a privilege to be at the forefront of neuroscience discovery at NIEHS. Dudek said she is very excited about Saha’s research work and looks forward to new discoveries stemming from this project. (Photo courtesy of Steve McCaw)

If a trainee’s goal is to successfully navigate the rocky highway of becoming a successful tenure-track lead researcher, the prestigious NIH Pathway to Independence Award (K99/R00) provides a paved on-ramp.

Ramendra Saha, Ph.D., a postdoc beginning his sixth year at NIEHS, became the latest beneficiary of this early-career support Oct. 1, when the National Institute of Mental Health announced his award. Because of action this year by the NIEHS Office of the Scientific Director, he will also become the first awardee to receive a merit increase of $2,000 to his training stipend (see text box). Saha is a member of the NIEHS Synaptic and Developmental Plasticity Group, headed by Serena Dudek, Ph.D.

This highly sought-after award offers new investigators two years of additional mentored training, and also provides for an additional three years of grant support that awardees take along to the institution of their choice. While most new hires are scrambling to use their startup funds to get preliminary data before the money runs out, K99/R00 grantees hit the ground with additional funds to support their research plan already in place.

Expanding understanding of early gene transcription

Saha’s work has focused on defining the mechanism involved in gene transcription induced by neuronal activity, building on findings that some genes, termed immediate early genes (IEGs), are transcribed extremely quickly after neuronal activity. After listening to a seminar by lead researcher Karen Adelman, Ph.D., another investigator at NIEHS working on chromatin signatures and Pol II poising on promoters for rapid transcription, Dudek and Saha hypothesized that IEG transcription downstream of neuronal signaling relied on Pol II poising on the promoters of these genes.

Saha’s research demonstrated their hypothesis was correct. Transcripts of IEGs that came up in the two-minute to five-minute period after neuronal stimulation did, indeed, have Pol II poising that allowed for such a fast response, and this research netted him a Nature Neuroscience paper (see story). During his time at NIEHS, Saha has been first author on several publications, received an NIH Fellows Award for Research Excellence in 2010 and 2011, and been recognized with competitive Society for Neuroscience awards.

Dudek said of Saha, “Ramen has never been short on ideas for his research, which makes me think he will continue to succeed in grant writing. Importantly, Ramen is also good at designing and doing experiments to test these ideas, and I know he will make a good PI [principal investigator/lead researcher].”

(John House, Ph.D., is a postdoctoral fellow in the NIEHS Genetics, Environment, and Respiratory Disease Group.)

Two phases of early-career support

The NIH Pathway to Independence Award consists of two parts and is one of the few available to non-U.S. citizens, as well as U.S. citizens. The K99, or mentoring phase, lasts up to two years and ends when the awardee secures tenure-track employment. This portion of the award supports mentored training and provides for career development, to prepare grantees for success and independence. The R00, or research phase, begins when the awardee becomes a tenure-track investigator. This is a non-renewable grant of up to three years that allows the individual to continue work toward establishing his or her own independent research program.

Saha’s K99 portion of the award starts immediately. NIEHS Scientific Director Darryl Zeldin, M.D., announced in September that successful grantees will also receive a monetary supplement to their training stipend during their K99 period, as a reward for their effort.

Saha’s mentoring will continue under Dudek. He will also have a co-mentor, NIEHS lead researcher Paul Wade, Ph.D., as he studies the electrophysiology of neuronal cells. His research proposal focuses on the histone H2A.Z, which has several isoforms and can be epigenetically modified. H2A.Z is a variant of histone H2A, and studies have shown that H2A.Z localization in chromatin tends to be higher near gene promoters. Saha aims to determine the role each variant plays in synaptic plasticity and gene transcription and, in turn, how this interaction affects the long-term synaptic plasticity involved in memory formation.

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