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Liao lab uncovers the structural basis of RNA-guided DNA degradation by Cascade and Cas3 - Aug 08, 2018

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Type I CRISPR-Cas system features a sequential target-searching and degradation process on double-stranded DNA by the RNA-guided Cascade (CRISPR associated complex for antiviral defense) complex and the nuclease-helicase fusion enzyme Cas3, respectively. The Liao lab has used single-particle cryo-electron microscopy (cryo-EM) to generate a near-atomic resolution structure of the Type I-E Cascade/R-loop/Cas3 complex, poised to initiate DNA degradation. This work, in collaboration with the Ke lab at Cornell University, was published in Science on July 6th. Together with their previous cryo-EM structures of CRISPR/R-loop (Xiao et al, Cell 2017, doi: 10.1016/j.cell.2017.06.012), their work provides a “molecular movie” that describes the entire course of action for target recognition, single strand nicking, and ATP-dependent DNA processing. The improved structural understanding now enables researchers to work toward modifying multiple types of CRISPR-Cas systems to improve their accuracy and reduce off-target effects in various biomedical applications.

Recent Faculty Promotion: Marcia Haigis - Jul 31, 2018

Marcia Haigis

Congratulations to Dr. Marcia Haigis on her promotion to Professor of Cell Biology!

Marcia's research uses biochemical, cellular, and mouse modeling approaches to systematically dissect the molecular regulation of mitochondrial functions during aging and age-related disease. In particular, her lab investigates how pathways that control aging, such as sirtuins, impact mitochondrial fuel utilization, bioenergetics and signaling. Learn more here.

Marcia Haigis selected to the Emerging Leaders in Health and Medicine Program - Jul 19, 2018

Marcia Haigis

Dr. Marcia Haigis has been selected for the National Academy of Medicine's Emerging Leaders in Health and Medicine Program. Congratulations, Marcia! The National Academy of Medicine was established in 1970 and works as a national leader to progress the field of medicine and medical policy. The Emerging Leaders in Health and Medicine Program fosters a community of leadership and innovation and chooses members based on their ability to mentor and potential to advance the future of medicine. Marcia was one in twenty named nationwide! Her lab studies the role of mitochondria in the aging process and age-related diseases. Learn more about her lab here.

Susan Shao named as a 2018 Vallee Foundation Scholar - Jul 17, 2018

Susan Shao

Dr. Susan Shao was just named a 2018 Vallee Foundation Scholar. Congratulations, Susan! The Vallee Foundation was created in 1996 by Bert and Kuggie Vallee, and its mission is to support outstanding young scientists who strive to advance their field with innovative and cutting edge techniques. The Foundation focuses on cultivating ingenuity and leadership through its worldwide programs. In addition to the Vallee Scholars program, the Foundation offers several programs to enhance research, including the Visiting Professorship Program and trainee travel fellowships. Susan's research focuses on the molecular mechanisms of protein quality control that are critical for maintaining cellular homeostasis; by studying the fate of newly synthesized proteins using biochemistry, structural biology, and cell biology approaches, her research will contribute to a better understanding of human diseases such as neurodegeneration and cancer. Learn more about Susan's research here.

Chouchani lab identifies a new molecular pathway for activation of adipose tissue thermogenesis - Jul 16, 2018

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The Chouchani lab has found in their most recent Nature paper that the anti-obesity properties of thermogenic adipose tissues can be activated by the mitochondrial metabolite succinate.  Thermogenic brown and beige adipose tissues can protect against metabolic disease, but require stimulation by external factors to do so.  The Chouchani lab found that these tissues selectively accumulate succinate upon activation of thermogenesis, and this is sufficient to activate their anti-obesity activity.  Mechanistically, succinate acts as a potent source of reactive oxygen species in these cells, which signal to activate thermogenic proteins.  Moreover, this newfound succinate pathway can be activated by dietary supplementation with succinate, which protects against diet-induced obesity in mice. 

Brugge lab discovers that tumor cells use the "wasabi receptor" TRPA1 to survive oxidative stress - May 29, 2018

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The Brugge lab has shown that the calcium channel protein, TRPA1, aids in tumor survival and has proposed targeting this protein as a potential cancer treatment. In a recent publication in Cancer Cell, the Brugge lab shows how TRPA1, normally used by humans as a sensor for environmental irritants such as wasabi or spicy mustard, is co-opted by tumor cells. Some cancers express TRPA1 in high levels, creating a defense mechanism against reactive oxygen species (ROS), thereby inhibiting programmed cell death and making cancer cells less vulnerable to radiation and chemotherapy. This research adds to a growing body of evidence that cancer cell survival can be improved by anti-oxidants. By further elucidating the biological mechanisms of TRPA1 function, the Brugge lab hopes to gain a better understanding of how this protein could be targeted in clinical cancer treatments. To learn more, visit HMS news.

Steve Liberles named as a 2018 HHMI Investigator - May 24, 2018

Steve Liberles

Dr. Steve Liberles was one of only 19 researchers across the country who were named 2018 HHMI Investigators.  He has made groundbreaking discoveries in the area of neural sensory systems, with his most research focused on the role of the vagus nerve and the many basic bodily functions it regulates, including breathing, satiety, and blood pressure.  Read more about his research here.  Overall, the 2018 Investigator class was well-represented by Cell Biology alums; other awardees include Dr. Gia Voeltz (former Rapoport lab postdoc) and Samara Reck-Peterson (former Cell Bio faculty member). 

Congratulations to Steve, Gia, and Sam!

Harper lab develops novel technique to observe ubiquitylation events - May 04, 2018

Alban Ordureau, a postdoc in the Harper lab, has developed a proteomics method that allows for the dynamics of PARKIN-dependent mitochondrial ubiquitylation to be followed with unprecedented preision and in a site-specific manner. The approach employed targeted proteomics of ubiquitylation sites in 15 PARKIN targets, allowing digital snapshots of PARKIN activity. This system was used to monitor PARKIN activity in stem cell-derived cortical and dopaminergic neurons, and to examine mechanistic aspects of the pathway.

This work was published in Molecular Cell (April 19th, 2018 issue). To learn more, see HMS News.

Kirchhausen lab develops new microscope that captures 3-D movies of cells inside living organisms - Apr 22, 2018

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The Kirchhausen lab, in collaboration with Nobel laureate and Janelia group leader Eric Betzig, has developed a microscope capable of capturing 3-D images and videos of cells inside living organisms in unprecedented detail. To enable such high resolution images, researchers combined two technologies: lattice light sheet microscopy, which Betzig developed in the early 2010s, and adaptive optics, a technique borrowed from astronomy. This work was published in a new study in the April 20, 2018 issue of Science. To learn more, read here.

Wade Harper named as a Fellow of the American Academy of Arts and Sciences - Apr 22, 2018

Wade Harper

Dr. Wade Harper, Chair of Cell Biology and the Bert and Natalie Vallee Professor of Molecular Pathology, was just named a 2018 Fellow of the American Academy of Arts and Sciences.  The mission of the Academy is to champion scholarship, civil dialogue, and useful knowledge.  It is one of the country’s oldest learned societies and independent policy research centers, and it convenes leaders from the academic, business, and government sectors to respond to the challenges facing the nation and the world.  Other notables named to this year's class include several Harvard-affiliated researchers, as well as Barack Obama and Sonia Sotomayor!  Congrats to Wade!

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