Dear colleagues,

Season’s greetings! I hope everyone is ready for the end-of-year holiday break. It has been a year like no other. Starting with the January 6 insurrection attempting to interfere with the transfer of power to a duly elected new president, followed by the onslaught of waves of coronavirus combatted by masks, social distancing, and the miraculous development of highly effective vaccines, and punctuated by both the conviction of the murderer of George Floyd and the stark evidence of the impact of climate change with devastating wildfires, flooding, and tornados. The last year has been exceptionally challenging, with long periods of interpersonal interaction limited to Zoom, interrupted by brief, joyous periods of unconstrained social interaction. We have learned new depths of resilience as well as how much we value friendship, family, and community, and one another’s company. Most remarkably, through it all we have stayed true to our mission, doing characteristically great science that has advanced our understanding of fundamental biology and human disease, particularly COVID-19. 

Remembering those we have lost

This year we lost a number of cherished and long-time scientific colleagues whose lives serve as exemplars of what a career dedicated to discovery, humanity, and truth can contribute. Neurophysiologist Victor Wilson, who first came to Rockefeller in 1953, died in January. Victor was best known for his work on the vestibular system, a structure in the inner ear that provides the brain information about the body’s movements and orientation. In March, we lost Mary Jeanne Kreek, a pioneer in the study of addiction and an energetic and beloved member of the community. Mary Jeanne joined Rockefeller in 1964 and played a prominent and passionate role in the establishment of methadone maintenance therapy in the 1970s, and in removing the stigma from addiction. Purnell Choppin, a pioneering virologist who was at Rockefeller from 1957 to 1985, went on to lead HHMI, where he helped build the investigators program—funding people, not projects—that would define the organization’s innovative approach to scientific investment. And in August, we lost T.P. King, a member of the faculty from 1952 to 2000, whose exceptional research greatly advanced the science and treatment of allergic reactions. We are fortunate to have had each of them as our friends and colleagues; their contributions to science and to society will long outlive them.

The COVID-19 pandemic

In the second year of COVID-19, we weathered a huge wave of cases from January through April of ’21. Vaccines were just being widely administered during this wave, and in New York City we saw at the peak 6,500 cases and 83 deaths per day. After a brief respite from the end of May to mid-July, the Delta wave hit NYC, and while cases peaked at ~2,000 per day, death rates were much lower, peaking at only 15 per day. And these deaths were 10-fold higher in unvaccinated people compared to those who were vaccinated, providing strong evidence of the vaccine efficacy. And just as the Delta wave was fading, to our immense frustration Omicron arrived virtually overnight last Monday. Omicron is a uniquely infectious version of the SARS-CoV-2 virus. With 30 mutations in its spike protein, Omicron is rapidly spreading through sub-Saharan Africa, Europe, and the US, with NYC being a leading edge of the US wave. It is clear that Omicron’s mutations impair the ability of antibodies from prior infection or vaccines to prevent infection. Nonetheless, two doses of the approved vaccines continue to provide significant protection from severe disease, and a third vaccine dose (booster) produces very high neutralizing antibody levels which are highly effective in preventing severe disease. While the clinical data is sparse as yet, unvaccinated people continue to account for the vast majority of hospitalizations and deaths from COVID-19. This is of particular concern in the US where 39% of the population remains unvaccinated. 

In the last week, new cases in NYC, which are now predominantly Omicron, have increased daily, from 3,800 positive tests reported on December 12 to 15,000 on December 19, nearly three times as many as reported at the peak of last January’s wave. We have seen a similar explosion of cases here on campus, despite our 99.8% vaccination rate. On December 6, we had 6 cases in the prior two weeks. As of this morning, we have 66, by far the highest number recorded throughout the pandemic. Moreover, there have been at least nine instances of likely transmission among lab members, compared to only one such transmission previously throughout the pandemic. Not surprisingly, 7 of the 8 viruses sequenced from this week’s cases were Omicron and only one was Delta. In just a few weeks, Omicron already accounts for 73% of all new COVID cases in the US. 

While there are many infections occurring in people who are vaccinated, including some who have had booster shots, booster shots remain exceptionally protective against hospitalization and death from both Delta and Omicron. For these reasons, everyone eligible should get a booster shot to minimize the risk of infection and get nearly complete protection from the risk of severe disease. To date, 1,050 members of our community have already received booster shots on campus, and many others have reported obtaining boosters off campus. If you received your booster off campus, please be sure to send a photo of your updated vaccine card to ruvaccinated@rockefeller.edu so OHS knows you’re protected. 

The extremely rapid spread of Omicron throughout NYC suggests that this wave could be very intense but relatively brief, as it has been in South Africa, where case numbers peaked within 4 weeks and have been coming down rapidly, though it is unknown how low case numbers will go. Please continue to take all precautions and stay safe through this extremely tough stretch. 

Looking ahead, there are new tools coming that will further reduce the risk of severe disease and death from COVID. Pfizer’s oral direct-acting antiviral protease inhibitor has been approved by the FDA today and will soon be available. It is highly effective in preventing severe disease and death in unvaccinated people if given in the first 3-5 days after the onset of symptoms. Coupled with widely available at-home or point-of-care testing, this could be a major tool to limit hospitalization and death from COVID. Of concern for the future, a reservoir of immunocompromised people who are chronically infected with SARS-CoV-2 seems the likely source of Omicron and for the future emergence of new, highly evolved viral variants. Effective treatment and/or prevention in this population should be of high global priority, and also underscores the need to focus on vaccinating the rest of the world in 2022. On balance, it seems likely that SARS-CoV-2 will become endemic in the population, causing typically less severe disease as population immunity grows. It may ultimately be handled like influenza, with periodic vaccination tailored to seasonal variants, administered to everyone or predominantly to those at highest risk of morbid outcome, backed up by direct-acting antivirals. Ideally, however, a universal pan-coronavirus vaccine, while challenging to achieve, could conceivably eradicate this threat.

University operations

Throughout the year, university operations have been critical to keeping the campus and our extended community safe. The staff of the CFC has provided a safe educational environment for young kids in our community. OHS and Bob Darnell’s lab have done tremendous work to provide sensitive saliva-based viral testing of the entire campus each week, and have performed contact tracing and clinical follow up for the community to identify early infections and prevent viral spread on campus. HR has greatly expanded mental health support to combat the challenges of social isolation throughout the pandemic. The Rockefeller Restart Committee continues to monitor trends and respond to changing guidance from the city and state, meeting as needed to consider whether changes to university policy are necessary to balance the risk of community spread against the inconveniences of the mandated precautions. In addition, the Emergency Preparedness and Response Committee meets every two weeks to review administrative support functions and campus operations. Plant Ops, Custodial, Housing, and Security have all played continuous roles in keeping the campus operational and safe. Finance and Procurement are keeping our bills (and paychecks) paid and our supply shelves stocked. The offices of Development and Investments continue to ensure resources are available for our mission. People in Academic Affairs, Sponsored Programs, Tech Transfer, Communications and Public Affairs, The RU Press, Planning and Construction and General Council have all adapted remarkably well to virtual and hybrid operations. Critical support for research is being provided by the Rockefeller University Hospital, the CBC and the talented staff at all of our scientific Resource Centers. In addition to all of their other responsibilities, Information Technology has helped with our Zoom license hosting over 100,000 virtual meetings since March 2020! We are extremely grateful to have so many dedicated and talented individuals among our colleagues keeping everyone safe and enabling pursuit of our scientific goals. 

Faculty appointments and promotions

On the faculty front, while we did not search for new faculty in 2020, we have an Open Search underway this year, and have narrowed the search to a group of 12 candidates who will give seminars and chalk talks in two symposia to be held in January and February. My thanks and appreciation to Nat Heintz, who has ably led this year’s search. Regarding faculty promotions, in the last year, Paul Cohen, head of the Laboratory of Molecular Metabolism, was promoted to associate professor, and Daniel Mucida, head of the Laboratory of Mucosal Immunology, was promoted to professor with tenure.

Board of Trustees

We have been exceptionally fortunate that throughout the pandemic our trustees have provided sage advice and guidance, and have been incredibly forward-thinking, generously supporting our COVID research and other initiatives of our Strategic Plan. Among these, Michael and Vikki Price are helping to establish the new Price Family Center for the Social Brain. Jim Simons, Pablo Legorreta, Bill Ford, Andreas Dracopoulos (through the Stavros Niarchos Foundation), Julian Robertson (through the Robertson Foundation), Barry Sloane (through the Fisher Foundation), Miriam Adelson, Karen Levy, and Joelle Kayden made leadership gifts to our COVID-19 research. Lew Sanders, Bill Ford, and Russ Carson are supporting renovation of three floors of the Bronk building for a Translational Center that will house an incubator for biotech start-ups and the Tri-Institutional Therapeutics Discovery Institute. And the Anna-Maria and Stephen Kellen Foundation, at the recommendation of trustee Michael Kellen and his wife, Denise, have funded a generous endowment for the Women and Science Entrepreneurship Fund. This support has been critical to advancing key areas of science throughout the pandemic and will carry our mission into the future.

Scientific advances

And all of these great efforts have provided the environment for the conduct of truly remarkable science.  In the last year, Rockefeller scientists have published a remarkable 848 peer-reviewed papers that have already been cited more than 4,600 times in the world’s literature.

Seventy-four papers published this year focused on COVID-19 and have been of great impact. Among these:

The team including Paul Bieniasz, Theodora Hatziioannou, Michel Nussenzweig, and Marina Caskey have published an amazing series of papers on the immune response to vaccination and natural infection. They showed the steep decline in neutralizing antibody levels after natural infection or vaccination with time, work that alerted us to the need for booster shots. They also showed how particular recurrent mutations in the spike protein of SARS-CoV-2 enabled escape from individual neutralizing antibodies, but showed that these individual mutations were not sufficient to substantially diminish effectiveness of vaccine-induced immunity. This inspired a follow-up experiment with a pseudovirus carrying 20 different recurrent mutations in the spike protein, which demonstrated that such an extensively mutated protein could evade immunity induced by vaccines, natural infection, or monoclonal antibodies. This study anticipated the emergence of an extensively mutated virus like Omicron. 

Consistent with vaccination providing protection from serious disease, Bob Darnell and colleagues published the first report characterizing the infection and clinical course of fully vaccinated people at high risk of severe disease who became infected with early versions of variant viruses, showing that patients could be infected, but had very mild clinical courses. 

Jean-Laurent Casanova’s lab identified rare mutations in TLR7, a key sensor of viral infection, as a cause of severe COVID-19 and demonstrated that antibodies against type I interferons- heralds of viral infection in the body- occur in ~4% of the elderly population and predispose to severe COVID, accounting for up to 20% of severe cases. This discovery has important implications that extend well beyond its implications for COVID-19.

Jeff Ravetch’s lab showed that modification of the Fc segment of monoclonal antibodies that direct them to selective engage activating Fcγ receptors results in improved efficacy of anti-SARS-CoV-2 MAbs in both preventing and treating disease in animal models. This also has important implications beyond COVID-19.

Charlie Rice’s lab published a method for cell-based replication of sub-genomic amplicons of the SARS-CoV-2 virus, permitting high throughput screens for direct-acting antiviral drugs. They also published identification of host gene products that are required for coronavirus replication, which could prove particularly challenging for viruses to overcome with viral genome mutations.

Mike Young’s lab showed the effects of chronic social isolation in fruit flies. They found that when alone for prolonged periods, they show impaired sleep and increased feeding, similar to effects seen in humans enduring social isolation during the COVID pandemic. They mapped these behavioral changes to particular neurons and circuits in the fly brain. This fascinating model provides the opportunity for new biological insights and ways to prevent or reverse these effects.  

Of course, COVID-19 research comprises just a fraction of our labs’ research output. Among the myriad important advances in other areas over the last year:

Kivanç Birsoy published a remarkable series of papers identifying metabolic vulnerabilities in cancer that can potentially be exploited via novel therapeutics. He has also identified novel aspects of mitochondrial biology, most recently identifying the mechanism by which the reducing agent glutathione enters mitochondria to prevent accumulation of reactive oxygen species.

Elaine Fuch’s lab has shown that long after recovery from an injury, non-immune cells such as epithelial cells and their stem cells carry chromatin marks at key genes that prime these cells for response to a repeated injury in the same location. 

Luciano Marraffini’s lab has discovered novel mechanisms by which type III CRISPR systems provide host defense against viral invaders. They have shown that infection induces production of a cyclic oligonucleotide whose binding to Card1 leads to activation of single stranded DNA and RNA nucleases, inducing dormancy of infected cells.

Gabriel Victora’s lab discovered that expression of the transcription factor FoxP3 in helper T cells shuts down their activity in the germinal centers of lymph nodes, where maturation of the antibody response to foreign antigens occurs, playing a key role in ending the maturation process.

Jeremy Rock’s lab has used CRISPR-based technology to ‘tune’ levels of expression of genes in the genome of the bacterium that causes tuberculosis (Mycobacterium tuberculosis) in order to identify essential genes that cause cell death when gene expression is only modestly reduced. These are particularly attractive targets for development of effective new therapeutics for Tb, which are desperately needed.

Paul Cohen and colleagues completed a remarkable study of 52,000 individuals who had ¹⁸F-fluorodeoxyglucose positron emission tomography scans, enabling evaluation for the presence or absence of brown adipose tissue (BAT), a highly metabolically active form of fat cells. The presence of BAT was associated with a lower prevalence of type 2 diabetes mellitus, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The results associate the presence of brown fat with many biomarkers of improved metabolic health.

Erich Jarvis is leading a consortium whose goal is to sequence and assemble the genomes of the 70,000 vertebrate species. This work will be foundational to understanding the evolution and biology of the highly diverse traits that characterize this vertebrate subphylum. This year the consortium published methodology for assembling high-quality reference genomes for the project and released assemblies of the first 25 species to emerge from the pipeline, along with fascinating observations from these diverse species.

Sohail Tavazoie and colleagues reported promising results from a phase I clinical study of an inhibitor of the creatine transporter in the treatment of metastatic colon cancer. His lab discovered that some cancers release the enzyme creatine kinase B, which transfers high energy phosphate from ATP to creatine, with the phosphocreatine then imported to supplement cellular energy, which is often limiting in the tumor’s hypoxic environment.  

Sebastian Klinge’s lab has determined the near-atomic level structure of 3 intermediates in the assembly of the small subunit of the ribosome in humans. This fantastically complex structure requires the function of dozens of proteins and an RNA dedicated to ribosome assembly. The results reveal the mechanisms of directional assembly of this essential element of protein-synthesis.    

Vanessa Ruta’s lab reported the structure of an insect odorant receptor bound to two chemically distinct activating ligands. The result showed that both chemicals bound to the same patch on the receptor, providing insight into the mechanism of channel opening and suggesting how a limited number of receptors can discriminate a vast number of odors.

Daniel Kronauer’s lab showed that clonal raider ants’ foraging behavior changes reproducibly as the size of the colony grows, demonstrating that the ants’ cooperative social behavior adapts in a predictable way to changes in group size.

Winrich Freiwald’s lab discovered neurons in the temporal lobes of primate brains that rapidly and selectively respond to faces of known individuals, explaining the instant recognition of a familiar face among a crowd of strangers.

This remarkable collection of scientific highlights represents just a tiny fraction of all that has occurred in our labs over the past 12 months. This research builds on a legacy of innovative discoveries that link us to the scientists who preceded us on campus dating back to our founding in 1901. In the last year we installed two new exhibits celebrating scientific discovery in Caspary Hall. The first, located just outside the entrance to Caspary Auditorium, honors Rockefeller recipients of major scientific prizes, including the Nobel, Lasker, Gairdner and Breakthrough prizes and the National Medal of Science (57 faculty and counting). The second display, in the Abby Lounge, honors the 23 winners of the Pearl Meister Greengard Prize, an annual international award presented to exceptional women scientists outside Rockefeller that was established by Paul Greengard and Ursula von Rydingsvard. Both exhibits have stunning designs, and I encourage you to stop by to reflect on some of history’s most memorable scientific achievements, the people who led these efforts, and their impact on human health.

Scientific recognition

The impact of the biomedical research done at Rockefeller has not gone unnoticed in the world’s science community over the last year. Both the Leiden Ranking and U-Multirank consortium funded by the European Commission have for the 7^th consecutive year found that Rockefeller ranks #1 in the world in the percentage of our papers that are in the top 1% and 10% of most cited papers in their fields, and that papers from Rockefeller are #1 in the world for the percentage of papers that are cited in patents filed by other institutions.

As another notable mark of recognition, in this year’s HHMI Investigator competition, three Rockefeller faculty, Vanessa Ruta, Daniel Mucida and Daniel Kronauer, were among the 33 faculty across the country appointed to these prestigious positions that provide unrestricted research funding for highly innovative biomedical scientists for 7 years, with the potential for continued support. In the last two such competitions, five Rockefeller faculty have been appointed HHMI investigators. Only Harvard, with six, has more, and only Stanford matched our total. This result is all the more remarkable given the small size of our faculty compared to these other institutions.

HHMI also named our colleague Leslie Vosshall as their incoming Vice President and Chief Scientific Officer, a position she will assume full-time in February 2022. Leslie will be leading HHMI’s Science Department portfolio, including the Investigator and Hanna Gray Fellows programs, among other initiatives. This is a critically important role for US biomedical science, and we all wish Leslie great success in her new job. I am delighted that Leslie will maintain her lab and professorship here at Rockefeller.

There have been many other awards that recognize Rockefeller faculty this year. These include the following:

The National Academy of Medicine elected to its membership three of our faculty: Mary Beth Hatten, Charlie Rice, and Leslie Vosshall. Mary Beth was elected for her foundational studies of cerebellar development that have broad significance for a wide range of brain diseases. Charlie was elected for his work leading to the discovery of direct-acting antiviral drugs that can cure virtually all patients with hepatitis C, a major cause of death from liver failure and cancer. And Leslie was elected for her studies of the mosquito Aedes aegypti, elucidating how this global disease-vector selects and feeds on the blood of human hosts. The election of Mary Beth, Charlie, and Leslie brings the number of Rockefeller faculty elected to NAM to 17.

Bob Roeder received the Kyoto Prize of Japan for studies revealing the molecular mechanisms of transcriptional regulation.

Cori Bargmann received the Salk Institute Medal for Research Excellence for discoveries into the relationships between genes, motivational states, and behavior.

Jean-Laurent Casanova received the Abarca Prize, presented by the King of Spain, for his discovery of mutations that predispose people to specific infectious diseases.  Jean-Laurent was also elected to the Belgian Royal Academy of Medicine.

Junyue Cao received an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award and an NIH Director’s New Innovator Award, both prestigious early-career awards that will fund his innovative research using single-cell genomic technologies. 

Katya Vinogradova also received an Irma T. Hirschl/Monique Weill-Caulier Trust Research Award and also received a Searle Scholar Award, both to fund her work using novel proteomic methods to identify therapeutic targets in immune regulation. 

David Allis received the inaugural Elaine Redding Brinster Prize from the Institute for Regenerative Medicine at the University of Pennsylvania for his discoveries of covalent chromatin modifying enzymes and their impact on gene regulation.  

Seth Darst received the Gregori Aminoff Prize for work investigating cellular systems for the production, transport, and quality control mechanisms of RNA.

Paul Cohen was named a National Academy of Medicine Emerging Leader in Health and Medicine.

Elaine Fuchs received the Bert and Natalie Vallee Award in Biomedical Science from the American Society for Biochemistry and Molecular Biology, for her discoveries on skin development and wound healing.

Viviana Risca has been named a Rita Allen Foundation Scholar.

Luciano Marraffini was named a member of the American Academy of Arts and Sciences.

Charlie Rice was elected to the National Academy of Inventors for his invention of novel methods for cell-based screening for direct-acting antiviral drugs. 

Kivanç Birsoy received the American Society of Cell Biology’s Innovation in Research Award for his novel approaches to discovery of metabolic vulnerabilities in cancers.

Luka Mesin, a postdoc in the Victora Lab, was named Blavatnik Regional Award Finalist in recognition is his work on B-cell maturation in the immune system. 

Josefina del Mármol, a postdoc in the Ruta lab, and Shiri Gur-Cohen, a postdoc in the Fuchs lab, were winners of the Tri-Institutional Breakout Award.

Diversity, equity, and inclusion

Turning to the Rockefeller Ph.D. program, there are now 252 students in the program, resulting from 41% of accepted students matriculating, an all-time high. Over the last five years, the number of students from underrepresented minority groups has increased by 85%, raising the percentage of the total to 20%. This includes an increase in the number of Black or African-American students from three to fifteen over this period. The number of women in the program has also increased by 39% and comprises 45% of the student body. 

Progress has also been made in increasing the diversity of the Rockefeller Board of Trustees. In the last year, eight new trustees have been elected, and include five women, three of whom are from diverse ethnic/racial groups. The university will benefit tremendously from the knowledge, expertise, perspective, generosity, and leadership of all of our new trustees.

The university has also added two new members of its executive leadership team.  Following the departure of our Chief Investment Officer, Amy Falls, to Northwestern University, we were fortunate to recruit Paula Volent as our new CIO and VP for Investments. Paula comes to us from Bowdoin College, following 20 remarkable years as their CIO. She arrived on campus in August and it’s already clear that she is a great addition to our community.

Ashton Murray will become our inaugural Chief Diversity Officer and Vice President for DEI. Ashton is joining Rockefeller from NYU Langone Medical Center where he is Director of DEI. He brings a wealth of experience in the areas of DEI programming, training, and community engagement, as well as a terrific background rooted in morality and ethics, with a master’s degree in divinity. As a member of the university’s executive leadership team, Ashton will work with academic and administrative leadership to promote an inclusive community and advocate on behalf of constituencies across the university. With his professional skills and experience, Ashton is well prepared to help us translate the university’s commitment into actions that will promote DEI and elevate our research, teaching, community engagement, and recruitment. I know we all look forward to welcoming Ashton to our community and to working with him to achieve these goals.

I’m grateful for the progress made in other DEI-related efforts, including increasing the diversity of seminar speakers, and hosting presentations on topics such as health disparities, racial disparities in outcomes associated with COVID-19, and racism in higher education and the scientific enterprise. A dozen presentations have taken place on campus over the past year in venues including the Friday Lecture Series, the Hospital seminar series, and the Anderson Cancer Center seminar series, as well as the DEI Journal Club hosted by RISI. Thanks to everyone who has put time and energy into this effort. There are also plans afoot led by Sohail Tavazoie, Daniel Mucida, Kivanç Birsoy, and others to host a symposium this summer to bring postdocs from underrepresented minority groups to campus to present and discuss their research and provide support and advice for their career directions.

Reflections and looking ahead

Reflecting on the last year, the pandemic has unquestionably demonstrated our ability to unite under challenging circumstances, displaying individual and collective resilience to rapidly respond to a public health emergency with incisive and innovative contributions. Our accomplishments are inspiring, and I’m so proud to be among such an amazing community. As we look to the coming year, there is much to be excited about. At the top of my wish list is sufficient control of the pandemic to effectively eliminate the social isolation we have been struggling with, enabling us to renew and enhance our sense of community that is so important to the fabric of Rockefeller and which has enriched the free flow of science across our campus.  As ever, I remain amazed by our scientific innovation and impact, and by the dedicated and supremely talented scientists among our faculty, staff, and trainees. Rockefeller continues to have outsized impact as we strive to honor our mission of Science for the benefit of humanity. 

I wish you and your families a joyful holiday and a restful winter break, and I look forward to seeing everyone and continuing our journey together in 2022. Please stay safe and take care of one another.

With all best wishes,

Rick