Connie Cepko

first_imgIn some ways, Connie Cepko’s job has gotten easier.The Harvard Medical School genetics professor is working to uncover the mysteries of the eye, to understand how it develops and what can go wrong. Her work ranges from understanding the genetic roots of diseases like retinitis pigmentosa, which afflicts 100,000 Americans, to basic genetic research using the latest technology.The work goes faster now than it once did because of major breakthroughs in genetics and information sharing made possible by the Internet. At the same time, there is an overwhelming amount of research needed to understand the complex interplay of genes involved in the development of the eye and the diseases that affect it.Cepko’s interest in this sort of work started long ago, sparked by a seventh-grade science fair. She grew yeast on agar plates, a completely new experience for her. Her experiment won first place and the attention of the judge, John Palmer, who ran a nearby laboratory.He invited her over to see the laboratory, and she found a new home. She grew up spending her Saturdays in his lab, which was dedicated to classifying tree fungi.“It was a fabulous experience and I just loved it,” said Cepko, who in addition to her HMS position is a Howard Hughes Medical Institute investigatorThere was no doubt about what she would study when she went to college at the University of Maryland. It had to be microbiology.She specialized in marine bacteria. That interest led her to the Massachusetts Institute of Technology for her graduate and post-doctoral work.Though she liked the field of virology, in which she worked for her thesis and postdoctoral projects, it felt crowded. It wasn’t the competition that bothered her, but the idea that so many people were spending their efforts on the same thing, she said. She looked for an area that was getting less attention and found the nervous system.Cepko started by studying the eye. She chose it because at the time it was an easy entry point for a rookie without a strong background in neurobiology. It was physically accessible and there were a lot of basics known about it.And yet, there was so much more to discover that she’s still at it today.There are 160 different genes that lead to blindness and it’s not clear what triggers the death of the affected photoreceptors, upon which vision relies.“Any little thing goes wrong and we go blind,” Cepko said.Researchers in her laboratory are trying to link genes with specific diseases and to better understand how the cells of the eye develop and what can go wrong along the way. Eventually, understanding what can go wrong may lead to new ways to intervene.When Cepko started, the only way to connect a gene to a problem was to painstakingly remove it from an organism. Researchers had to breed mice without the gene in question. But today, advances in RNA interference allow researchers to create bits of RNA that attach to a messenger RNA, efficiently blocking the function of a gene so researchers can see what happens without it.By using the RNA interference process over and over again on different genes, researchers are collecting the pieces of a giant jigsaw puzzle whose image is a better understanding of the eye and the diseases that attack it. With the advances in science, more pieces are falling into place.“Now, we have clues. We have many pieces of the puzzle,” she said. “Before, we had a 1,000 piece puzzle but only a few border pieces.”The explosion of the Internet fosters the work because information and advances in other laboratories are more readily available. Researchers can quickly absorb the latest advances in other laboratories and apply them to their own research.While her laboratory looks at the bigger picture of what makes a rod cell or a cone cell or another piece of the eye, it’s also tackling the specific problem of retinitis pigmentosa.The disease affects 1 out of 3,000 people. It’s a genetic ailment that affects the rods of the eye, used to see in near darkness. Perhaps most vexing is that once the rod cells die, the cone cells, which are used for all of our daylight vision, also start to die even though they don’t have a genetic defect.It’s not clear how the genes cause the rod cells to die or why the cone cells follow.Researchers in her lab are trying to get a better understanding of what happens as the disease takes its toll. They are looking at what genes change in their expression during different stages of the disease. A postdoctoral fellow, Claudio Punzo, began their work in this area, and has recently published his findings in Nature Neuroscience. His work has provided a totally new view of the disease, and suggests that the cone cells might be starving, and then undergoing autophagy, a form of self-digestion. Bo Chen, another postdoctoral fellow, working on what might keep the rods alive, has found that the addition of a gene encoding histone deacetylase 4 promoted rod cell survival far longer than in untreated animals. These clues are giving the group ideas on novel therapeutic targets to help prolong vision in individuals who are genetically predisposed to go blind.There is serious work going on in her lab, but there is a collegial atmosphere, said Jeffrey Trimarchi, a post-doctoral fellow who has been working with Cepko for five years.There are four Ph.D. candidates and nine post-doctoral students in the lab. Cepko chooses not only good scientists but also good people, Trimarchi said.“It’s important to have people in the lab who get along,” he said. “You need to have people who will share what they’re doing and be willing to talk about their work.”In some ways, she is hands off, letting researchers go in their own direction. At the same time, she works with them to put what they are doing into context.Trimarchi said he had heard good things about Cepko’s lab when he was looking for a place to do his post-doctoral studies, but it was talking with her that convinced him.“When I sat down with her, the ideas kept coming, one right after the other,” he said.She keeps a white board in her office and uses it frequently for brainstorming.While her primary focus is on basic research, Cepko keeps in mind potential real-world applications. She promotes that concept as co-director of the Leder Medical Sciences Program, which integrates the Ph.D. students with Harvard Medical School.Participants take courses covering the basics of human biology and disease. They focus on organ systems and diseases ripe for investigation and novel therapeutic approaches. At the same time, they attend clinical conferences, participate in the Mentored Clinical Casebook program and attend workshops, lectures and other dinner series with people who work at the interface of basic science and clinical medicine, from all different venues.“It offers them another perspective and lets them consider the possible applications of their laboratory work,” she said.last_img read more

Last Call for 11 (!) Broadway Shows Closing in January

first_img View Comments It’s a new year and a new decade, which means Broadway is getting ready to make more compelling entertainment for the millions of people who flock to the Great White Way yearly. Unfortunately, some shows have to close to make room for the new ones coming in. In January, a whopping 11 shows will be taking their final bows. Check out everything you absolutely must see before the end of the month.  Chris McCarrell in The Lightning Thief. (Photo: Jeremy Daniel) The cast of A Christmas Carol. (Photo: Joan Marcus) JANUARY 5: The Final QuestThe Lightning Thief: The Percy Jackson Musical will journey on its last Broadway quest on January 5. The show’s limited engagement arrived on the Great White Way three years after it made its off-Broadway debut, and fans of the popular Rick Riordan young adult series welcomed it with open arms. Chris McCarrell, the only cast member not making his Broadway debut in the show, has played the title character since the beginning. It won’t be long before lightning strikes again because the musical is hitting the road to bring Percy’s story of bravery, acceptance and love to cities across the country.  Mary-Louise Parker Star Files Katharine McPhee and Caitlin Houlahan in Waitress. (Photo by Emilio Madrid for January 5: One More CarolThe first Broadway production of Charles Dickens’ A Christmas Carol will help ring in the holiday cheer one last time on January 5. With an adaptation by Tony winner Jack Thorne, the new take on the classic transported audiences back in time with the help of Campbell Scott’s portrayal of Ebenezer Scrooge. Cookies, string quartets and a theater full of lights allowed audiences to revel in the holiday spirit and hear the beloved Christmas story in a new way.  James Cusati-Moyer Andrew Barth Feldman (Photos: Emilio Madrid and Matthew Murphy; Composite by Ryan Casey for The cast of Oklahoma! (Photo: Little Fang) The cast of Slave Play. (Photo: Matthew Murphy) Ato Blankson-Wood Katharine McPhee JANUARY 5: Red Sequins Are ForeverThe musical comedy, based on the 1982 film of the same name, will play its final performance on January 5. Tootsie follows Santino Fontana as Michael Dorsey, an unemployable actor who disguises himself as a woman to land a job. Needless to say, hilarious chaos ensues. The show received 10 Tony nominations and took home two: one for Fontana’s star turn and the other for scribe Robert Horn. Sad you missed it? Tootsie will soon embark on a national tour, so you’ll be able to see the unstoppable Dorothy Michaels in a town near you. JANUARY 19: Keep ListeningJeremy O. Harris’ buzzed-about Broadway debut work Slave Play will end its extended limited run on January 19. After Harris wrote the provocative piece while still in graduate school, it had its world premiere at off-Broadway’s New York Theatre Workshop in 2018 before moving to the Golden Theatre. Following three interracial couples as they discover truths hidden deep within themselves, Slave Play’s impact will be felt for a long while. ALSO:JANUARY 4: Derren Brown: Secret will do its final trick at Broadway’s Cort Theatre.JANUARY 5: The Illusionists—Magic of the Holidays bows for the last time at the Neil Simon Theatre.JANUARY 5: The last snowfall will happen at the Stephen Sondheim Theatre in Slava’s Snowshow.JANUARY 5: The acclaimed Yiddish production of Fiddler on the Roof will close at Stage 42.JANUARY 5: Alexis Scheer’s Our Dear Dead Drug Lord, which received three extensions off-Broadway, ends its run.JANUARY 19: Samuel D. Hunter’s Greater Clements, starring Judith Ivey, closes at the Mitzi E. Newhouse Theater.JANUARY 26: Current Dear Evan Hansen  stars Andrew Barth Feldman and Alex Boniello, who play Evan Hansen and Connor Murphy, respectively, will take their final bow at the Music Box Theatre.  Will Hochman JANUARY 12: Mic DropWhat started out as a side hobby during the creation of In the Heights, Freestyle Love Supreme has turned into its very own verifiable Broadway hit. Created by Lin-Manuel Miranda, Thomas Kail and Anthony Veneziale, FLS combines rap and improv, so no one can see the same show twice. With occasional surprise appearances by Miranda, Wayne Brady, Christopher Jackson, Daveed Diggs and more, this is a Broadway event that must be experienced to be believed, so be sure to get to the Booth Theatre by January 12.  Ali Stroker The cast of Freestyle Love Supreme. (Photo: Joan Marcus) JANUARY 12: Turning the PageAdam Rapp’s Broadway debut thriller The Sound Inside will play for the final time at Studio 54 on January 12. The two-hander, directed by David Cromer, follows a professor and student’s complicated relationship that blurs the line between fiction and reality. Featuring newcomer Will Hochman and Tony winner Mary-Louise Parker, this beautifully performed piece is quietly intense and literary, while leaving audiences stunned.  Alex Boniello Chris McCarrell Santino Fontana in Tootsie. (Photo: Matthew Murphy) JANUARY 19: Chili To-GoDaniel Fish’s Tony-winning revival of Oklahoma! will serve chili and corn bread to its final audience on January 19. Starring Damon Daunno, Rebecca Naomi Jones, Mary Testa, Patrick Vaill and recently crowned Tony winner Ali Stroker, this newly imagined version of the Rodgers and Hammerstein classic has been surprising audiences at the Circle in the Square Theatre for 10 months. With history-making performances, a thrilling dream ballet and hearty snacks during intermission, Oklahoma!’s absence is sure to be felt.  Santino Fontana JANUARY 5: Goodbye PieComposed by singer-songwriter Sara Bareilles, Waitress will finish its Broadway run on January 5. Waitress garnered four Tony nominations and has gone on to play across the country and in the West End. With a treasure trove of casting replacements like Katharine McPhee, Jeremy Jordan, Gavin Creel, Jordin Sparks, Colleen Ballinger, Todrick Hall and even Bareilles herself, Waitress has given fans many reasons to return during its almost four-year shift at Broadway’s Brooks Atkinson Theatre. McPhee will be the show’s final Broadway Jenna by finishing out the run. Will Hochman and Mary-Louise Parker in The Sound Inside. (Photo: Jeremy Daniel) View All (10)last_img read more