I am delighted to announce that yesterday, the Rockefeller Board of Trustees’ Committee on Scientific Affairs voted unanimously to approve promotions of three Heads of Laboratory: Agata Smogorzewska, Greg Alushin, and Li Zhao. All three promotions are effective July 1.
Agata Smogorzewska has been promoted to Professor with tenure and Head of the Laboratory of Genome Maintenance. She has developed a strong research program focused on understanding the mechanisms of repair of DNA damage and the consequences of its failure. To gain insight into this process, she has studied Fanconi Anemia (FA), an inherited disease in which crosslinks between the two DNA strands aren’t normally repaired, preventing DNA replication across these sites. Patients with FA develop bone marrow failure, are predisposed to a variety of cancers, and have variable congenital anomalies.
By clever cell-based screens for sensitivity to DNA crosslinking chemicals and genomic sequencing of FA patients, Agata has discovered numerous genes whose mutation prevents DNA crosslink repair, and has determined their biochemical mechanisms, showing their roles in specifying the site of DNA crosslinks and recruiting the specific enzymes that chop out the damaged bases to allow their replacement. She has also identified genes that are essential for protecting the stalled DNA replication fork while repair is being accomplished and has shown how still other proteins act to stop stalled replication and how they are removed to restart replication after DNA repair has been accomplished.
She has also shown that patients with FA who develop head and neck cancer have a unique DNA signature featuring a high frequency of DNA deletions, duplications, and rearrangements affecting genes that drive carcinogenesis. This provides strong evidence that FA patients are particularly prone to damage from environmental agents that drive this cancer. Because crosslinks are commonly caused by aldehyde metabolites of ethanol and tobacco smoke, alcohol consumption and smoking are likely of particularly high risk for these individuals.
Aside from her scientific accomplishments, Agata is an outstanding and engaged mentor who sets high expectations for her trainees. She directs the Mammalian Genetics and Genomics graduate course, and has received the Rockefeller University Distinguished Teaching Award for this contribution. She has long been involved in the Tri-Institutional Medical Scientist Training Program and is currently Associate Director of this program. She also is a long-serving member of the Institutional Review Board that governs human subjects research at Rockefeller, and she serves on the Advisory Committee for Clinical and Translational Science (ACCTS).
Beyond Rockefeller, Agata serves on the Scientific Advisory Boards of the Jane Coffin Childs Medical Research Fund and the Fanconi Anemia Research Fund. Reflecting her stature in the field, she has chaired or co-chaired many international meetings on DNA replication and repair including the Keystone Symposium on Genome Maintenance and the Gordon Conference on Replication, Repair and Architecture. She is incoming co-chair of the annual Cold Spring Harbor Meeting on DNA Replication and Genome Maintenance.
Agata has received a number of prestigious awards and recognitions. For her Ph.D. research, she received the Harold M. Weintraub Graduate Student Award. She has also received the Burroughs Wellcome Fund Career Award for Medical Scientists, the Doris Duke Charitable Foundation Clinical Scientist Development Award, the HHMI Faculty Scholar Award, and she is an elected member of the American Society for Clinical Investigation.
Greg Alushin has been promoted to Associate Professor and Head of the Laboratory of Structural Biophysics and Mechanobiology. He is pursuing the hypothesis that actin cables in cells are mechanosensors, perceiving changes in mechanical forces acting on cells and entraining adaptive cellular responses. He has made original observations that support this idea.
For example, he showed that in vitro, the LIM domain transcription factor FHL2 switches from being unbound by F-actin that is not under stress, to being fully bound by F-actin under mechanical stress. This occurs in cells as well: On a rigid surface, F-actin is under mechanical stretch and FHL2 is sequestered in the cytoplasm, preventing its nuclear function in transcriptional regulation. Cells grown on soft substrates do not bind FHL2 and it localizes to the nucleus. Greg has proposed that this interaction can regulate cell proliferation, which is low on a substrate of low rigidity and high on a rigid substrate. He has shown similar alterations in binding of alpha-catenin to F-actin under force. He has also shown that the force of actin polymerization and stretching by myosin motors produces distinct states that are distinguishable.
Greg has also developed original approaches to analysis of cryo-EM data to determine the structural determinants of actin binding proteins to its F-actin targets as well as the impact of actin filament bending on helical pitch and facial interfaces of actin monomers. He has also shown that in addition to mechanical loading, different nucleotide states of F-actin (i.e., bound to ADP or ADP- Pi) change filament flexibility and alters interactions with actin binding proteins.
Beyond his research activities, Greg is the co-organizer of Rockefeller’s graduate Biophysics and Quantitative Biochemistry course and lectures each year in Rockefeller’s Cell Biology course. In 2021, he received The Rockefeller University Distinguished Teaching Award. He also has a strong funding history with a record of continuous, independent federal funding since his Rockefeller appointment.
Greg has received numerous awards for his research, including the Harold M. Weintraub Graduate Student Award, the Norton B. Gilula Award from the American Society of Cell Biology, the Forbes 30 under 30 in Science and Healthcare, the Pew Biomedical Scholar Award and a Presidential Early Career Award for Scientists and Engineers.
Li Zhao has been promoted to Associate Professor and head of the Laboratory of Evolutionary Genetics and Genomics. She is an evolutionary biologist who combines superb training in computational biology and bench research to study the origins of de novo genes—DNA sequences that are transcribed and produce protein products that have apparently evolved from previously functionless DNA sequence.
Li has identified over a thousand potential de novo genes in Drososphila that she has shown are recently evolved and are transcribed into RNA, and she has shown by mass spectrometry that they are also translated into proteins that are predicted to fold into stable three-dimensional structures. She has shown that these genes are preferentially expressed early in development of spermatocytes, suggesting a possible source for selection to act.
In another surprising discovery, she modeled the 3D structures of the protein coding sequences of several de novo genes as their primary sequences evolved, discovering that changes in primary amino acid sequences were rarely accompanied by significant departures from the earliest 3D structures. This implies very early emergence of a functioning protein that is only modestly tuned subsequently. Her use of mass spectrometry proved that a large fraction of apparent de novo genes produce mature protein products. In fact, she identified nearly 1,000 cases in which open reading frames associated with de novo genes were definitively translated into peptides.
Li has been a terrific mentor and leads a journal club for first-year graduate students in Computational Biology and Medicine. She serves on the Rockefeller University Graduate Admissions Committee, the Faculty Open Search Committee, the Friday Lecture Series Selection Committee, and the Rockefeller University Postdoctoral Awards Review Committee. She has also organized a number of prestigious meetings and sessions at meetings discussing topics in evolutionary biology.
Li has received a number of awards including a Merit Award from the Chinese Academy of Sciences for her Ph.D. research, an Alfred P. Sloan Research Fellowship, and she has been named a Vallee Foundation Scholar and an Allen Brain Institute Distinguished Investigator, and has received a prestigious MIRA/R35 award from the National Human Genome Research Institute of NIH.
These three faculty members are exceptional scientists leading highly productive and impactful laboratories. They are all recognized as leaders in their fields and great contributors to the Rockefeller and broader scientific communities.
Please join me in congratulating these three terrific scientists on their well-deserved promotions!
With best wishes,
Richard P. Lifton, M.D., Ph.D.
Carson Family Professor
Laboratory of Human Genetics and Genomics
The Rockefeller University