“Larschan’s work has already distinguished her as a scientific pioneer…”
“It was so exciting,” Larschan says of the effort, which began in 1990 and was completed in 2003. Scientists on the project “thought they were going to have everything figured out,” she recalls.
Larschan began figuring out her own path while pursuing an undergraduate degree in biochemistry from Wellesley College and working summers in a cancer lab at Harvard Medical School. And in earning a Ph.D. in genetics from Harvard and continuing training at Brigham and Women’s Hospital, Larschan discerned the fate of her research goals: to uncover connections between gene expression and disease.
She now runs her own research lab focusing on transcription factors, molecules that bind to DNA sequences. In so doing, they orchestrate which genes are turned on and which are silenced in various cells types and under an array of conditions, such as health and disease.
As one of the 22 early-career scientists named Pew Biomedical Scholars in 2011, Larschan studies the role of transcription factors in a phenomenon that allows male organisms to survive with only one X chromosome. While females have two copies of the X chromosome, males have one X and one Y chromosome, which houses only genes associated with male fertility.
At first blush, the males’ lack of a second X chromosome ought to be lethal. Human cells have 46 chromosomes—two sex chromosomes and 22 paired sets of so-called somatic chromosomes, which contain genes related to non-reproductive bodily systems. Organisms need both copies of each somatic chromosome pair to live.
So what keeps males alive in the absence of a backup X chromosome? In a telling model, male fruit flies manufacture a specialized transcription factor called MSL (short for male-specific lethal—as they would die without it).
This, Larschan’s lab has discovered, enables them to double the genetic expression from their sole X chromosome—an advantage that might also appear in human males. Her group employs novel techniques to measure the moment-to-moment activity of genes on fruit flies’ X-chromosomes. MSL, they’ve found, helps enzymes to copy those genes.
If—in the distant future—that discovery proves applicable to humans, Larschan foresees that biomedical scientists might better understand and one day treat diseases such as cancer or schizophrenia, which are associated with abnormal gene regulation.
But for now, Larschan’s work has already distinguished her as a scientific pioneer, earning her a Presidential Early Career Award for Scientists and Engineers in 2012. That honor, bestowed by the President, recognizes researchers who take risks at the frontiers of science and technology.
Larschan passes that same eagerness to innovate on to her students. For instance, she teaches a transcription seminar which zeroes in on an initial step of the mechanism that allows all cells to create proteins from the blueprints in their genes.
In exposing genetics’ next frontier to her students, Larschan hopes to share the excitement for science the Human Genome Project instilled in her—and that her Pew award now nurtures. “It’s fun to get people started on a career in scientific inquiry,” she says.
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Since 1985, Pew’s biomedical programs have been supporting promising beginning researchers in the health sciences—particularly young investigators with innovative approaches and ideas. This article is the second in a “Biomedical Researcher of the Month” series highlighting Pew’s biomedical programs.
- Date added:
- Jan 22, 2013
On May 9, the Howard Hughes Medical Institute (HHMI) announced that 27 of the nation’s top biomedical researchers—including seven Pew scholars—will become HHMI investigators and will receive the flexible support necessary to move their research in creative new directions. The Pew scholars named HHMI investigators are Peter Baumann (2003), Michael Dyer (2004), Nicole King (2004), Tirin Moore (2004), Dyche Mullins (2000), Michael Rape (2007), and Rachel Wilson (2005).More info
2009 Pew Biomedical Scholar Charles Mullighan was part of a research team at St. Jude Children's Research Hospital which recently found mutations responsible for more than half of a subtype of childhood brain tumors. Their paper in Nature Genetics pinpointed alterations in two genes that increased the risk of low-grade gliomas—the most common childhood tumors of the brain and spinal cord—and identified an existing drug as a possible treatment.More info
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Jeff Gore, a 2011 Pew Scholar and assistant professor of physics at MIT, has been awarded a four-year, $1,131,603 grant from the National Institute of General Medical Sciences – one of the 27 National Institutes of Health – to pursue research into cooperation and cheating in the evolution of antibiotic resistance in bacteria.More info
Ben Stanger, a 2009 Pew scholar and assistant professor at University of Pennsylvania’s Perelman School of Medicine, has demonstrated that cells can change their identities under normal conditions in the body. In a study published in Genes and Development, Dr. Stanger pinpointed the gene that allows the main type of liver cells in mammals to convert into the cells lining bile ducts.More info
To understand how embryos develop, many researchers look to animal models such as worms and frogs. But Mary Gehring, a 2011 Pew Biomedical Scholar and assistant professor of biology at the Massachusetts Institute of Technology, turns to plants—even weeds.More info
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Dinu Florin Albeanu, a 2012 Pew Scholar, was profiled in National Geographic’s “Only Human” series, which highlighted his success as a Romanian scientist. Having lived in Bucharest for most of his life, Dr. Albeanu recognizes the challenges facing Romania’s scientific enterprise. Since relocating to the United States, the assistant professor of neurology at Cold Spring Harbor Laboratory has co-founded a summer program for aspiring neurologists in Romania. More info
2011 Pew Scholar Wins Paul Allen Distinguished Investigators Award to Unlock Fundamental Questions in Biology
Jeff Gore, 2011 Pew Scholar and assistant professor of physics, Massachusetts Institute of Technology, has won the Paul Allen Distinguished Investigators Award to Unlock Fundamental Questions in Biology. The award, announced today by the Paul G. Allen Family Foundation, provides $7.5 million in exploratory grant funding to a carefully selected group of scientists who will embark on five new pioneering research projects that aim to unlock fundamental questions in biology. Dr. Gore will use single-celled yeast to explore how ideas from game theory can provide insight into cellular decision making.More info
Dr. Michael "Micha" Rape, a 2007 Pew Scholar, has been named winner of The Vilcek Prize for Creative Promise in Biomedical Science for his work on ubiquitination, a process which "tags" damaged or bad proteins for destruction, as it relates to many diseases, including cancer or neurodegeneration.More info
Ben Stanger, named a Pew biomedical Scholar in 2009, co-authored a paper in Genes and Development describing a master regulator protein, which may explain the development of aberrant cell growth in the pancreas spurred by inflammation.More info