Discovering gene regulatory mechanisms underlying genomic imprinting and functions of imprinted, non-coding RNAs in neurophysiology and disease
Genomic imprinting results in the preferential expression of a gene from either the maternal or paternal allele. Nearly all imprinted domains express non-coding RNAs, including long and small non-coding RNAs, in a parental biased manner. Yet the physiological functions and molecular mechanisms of these imprinted transcripts are poorly understood. With a focus on imprinted transcripts highly expressed in neurons, we seek to understand how parental gene inheritance influences gene expression in the brain through the activity of non-coding RNAs.
We have established an in vitro system that enables detection and manipulation of allele-specific expression in neurons. We are using this system to (1) delineate the neuronal networks regulated by imprinted microRNAs, (2) identify the neuronal targets of imprinted orphan small nucleolar RNAs, and (3) build a mechanistic understanding of cis regulation by imprinted long non-coding RNAs.
Imprinted disorders arise from inappropriate genetic alterations within imprinted domains. We have previously shown that targeting an imprinted long non-coding RNA is a viable therapeutic strategy for the treatment of an imprinted disorder, Angelman syndrome. Our laboratory is expanding on this work by examining the physiological role of imprinted non-coding RNAs during normal and dysregulated neurodevelopment.
Lab News
The Whipple Lab welcomes MCO graduate student Isra Galicia Silva to the lab. She received her B.S. in Biochemistry and Microbiology from the Universidad del Valle de Guatemala and completed a Post-Baccalaureate at the University of Pennsylvania, where she worked with the J-Rad Lab on the interplay between metabolism, circadian rhythms, and cellular maturation.
Congratulations to Min Bae on receiving a postdoctoral fellowship award to further study how the Mest-Copg2 ICR achieves long-range regulation.
The Whipple Lab welcomes our newest member, Katherine Gu. Katherine joins us as a research assistant. She received her B.A. in Biochemistry and Chemical Biology from Vanderbilt University. Outside of lab, she enjoys working out, hiking, and trying restaurants in the Boston area.
Congratulations to Carlie McGrath Tydings who will be joining the Greenleaf Lab at the Stanford Department of Genetics in July, as a research assistant.
Congratulations to Aditya for graduating from Harvard! He will be attending graduate school at MIT in the fall.
Lily will be part of Harvard’s Program for Research Science and Engineering (PRISE) this summer. Her project with the Whipple lab will involve observing hallmarks of nucleolar stress and the role of small nucleoar RNAs on neuronal function.
Congratulations to Research Assistant Jen Yi! This fall, Jen will begin graduate school in the Harvard MCO program.
Debaleena Kar has joined the Whipple lab as a Postdoctoral Fellow. Her research focuses on the role of snoRNA in translation.
Daniel successfully defended his PhD thesis work on "Investigating the cis-regulatory mechanisms underlying neuronal imprinted expression." We thank Daniel for all his contributions to the lab and wish him the best of luck in his next career steps at Intellia Therapeutics!
This grant aims to investigate the role of SNORD116 in ribosome biology. For more details on this project and others funded by FPWR, a blog with the funded descriptions and a link to the recorded webinar presented by Dr. Theresa Strong, Director of Research Programs at FPWR can be found here.
A new study led by Daniel Loftus of the Whipple Lab has found that differences in maternal and paternal genomes in embryonic stem cells shape gene expression in neurons. The study, which appears in the latest issue of the journal Genes & Development, delves into the 3D structure of a genome region called Peg13-Kcnk9.
The Whipple lab enjoyed the MCB fall kick off celebration to welcome new students on campus. Graduate students interested in rotating should contact Amanda Whipple.
Congratulations to Courtney Whilden for being awarded an NIH F31 fellowship! This award will support her project on snoRNAs.
Carlie has been awarded HCRP (Harvard College Research Program) funding to pursue her work on the subnuclear localization of imprinted genes in the lab this summer.
Udbhav Chitta was the first member of the Whipple lab in 2019 and has been accepted into the biomedical graduate program at UMass Medical School. We are grateful to his contributions to the lab and are excited he will remain nearby. Warm wishes!
While he will be sorely missed in the Whipple lab this summer, we are proud of Aditya for seizing this opportunity to widen his skill sets. Look out for his graduate school applications this fall!
The HCRP will fund Carlie's independent research in the Whipple lab to investigate subnuclear localization of imprinted loci.
Aditya Wirawan presented his research at the National Collegiate Research Conference. Watch out for his graduate school applications this fall!
Join us in welcoming Amanda Leinbaugh to the team! Amanda will provide administrative support for Dr. Whipple and the lab.
We bid a warm farewell to Daniel Blackwell as he follows his dreams in LA. We thank Daniel for helping us with the administrative side of getting our lab up and running since 2019.
This award will support the work of graduate student Courtney Whilden on "Investigating Satiety Circuitry Changes in Prader-Willi Syndrome." Experiments are already underway!
MCB faculty Amanda Whipple has received an R35 Maximizing Investigators’ Research Award (MIRA) from the NIH. The award provides five years of funding to promising early career PIs, with the goal of ensuring recipients’ stability and flexibility as their labs branch out in pursuit of new research questions…
Congratulations to Aditya on his successful presentation at the Harvard Undergraduate Research Opportunities in Science fair today.
We are welcoming a new undergraduate in the lab, Carlie McGrath, a junior concentrating in Integrative Biology. Carlie will be working under the mentorship of Min on gene regulatory mechanisms controlling imprinted gene expression.
The Whipple lab is now accepting applications for a Research Assistant. Please apply through the Harvard jobs portal linked above.
Simon joined the Whipple lab in 2019 as an undergraduate, completed his senior thesis, and then following graduation worked full-time as a Research Associate. In addition to keeping the lab operating smoothly, his experimental and computational work was critical to our ongoing studies on snoRNAs. He will be sorely missed by all, but we're looking forward to a lab reunion in Austria some day!
Areas of interest: RNA biology, neurobiology, computational biology
Our work balances hypothesis-driven research using established methods with exploratory research using new high-throughput methods. This enables us to test data driven models while remaining open to unexpected, paradigm-shifting discoveries. Read our ad here.
The Herchel Smith Harvard Undergraduate Research Program is a competitive award supporting a select group of high-potential undergraduates conducting a promising summer research project. Aditya will continue working in the Whipple lab on an independent project to identify novel snoRNA binding proteins in neurons.
We thank Thareendra De Zoysa for his contribution to all aspects of the Whipple Lab. As the first postdoc in the lab, he served to greatly enhance both our science and our lab environment. He made significant contributions to identifying targets of orphan snoRNAs. Thareendra will be missed by all but we are so excited for his future!
Congratulations to Courtney Whilden for receiving the Simmons Award from the Harvard Center for Biological Imaging. Courtney will use these funds to support snoRNA imaging experiments.
We aim to build mechanistic models of the cellular and physiological activity of imprinted non-coding RNAs, including microRNAs, small nucleolar RNAs, and long non-coding RNAs.
We are a collaborative group of scientists seeking to uncover new regulatory roles of RNA in the cell. Read our mission statement and learn more about who we are.
We are expanding our team! We aim to build a multidisciplinary group from diverse backgrounds, including computational biologists, molecular biologists, and neuroscientists.