EXAMPLE REPORT: Montserrat and Vladimir Fencl Endowed Research Fund
at Harvard Medical School
Benefactor Report
October 2025
Table of Contents
01.
Dean Daley
Note of Thanks
03.
Featured Research
02.
Research at HMS
Learn More
Stuart Orkin
Arlene Sharpe & Gordon Freeman
Isaac Chiu
Bob Datta
Montserrat and Vladimir Fencl Endowed Research Fund
Letter from the Dean
October 9, 2025
Dear Dr. Fencl,
I’m delighted to thank you for your generosity to Harvard Medical School and pleased to share a report highlighting some of the School’s recent notable biomedical research. The Montserrat and Vladimir Fencl Endowed Research Fund will support a wide range of research on the HMS Quad for generations to come. In the coming years and decades, this work will lead to many groundbreaking discoveries and therapies like those described here.
This is a moment of tremendous uncertainty for medical and scientific research. With the future of federal funding in question, philanthropy matters more than ever to pioneering faculty scientists like Stuart Orkin, Arlene Sharpe, Gordon Freeman, Bob Datta, and Isaac Chiu. Philanthropy has always played a crucial role in advancing research into little-studied questions, rare diseases, and early-stage ideas. Today, your support matters more than ever, helping our scientists turn breakthroughs in basic science into transformative new therapies.
Your commitment will empower our researchers to improve the health of individuals and communities and advance the cause of science. Without your generosity, this work cannot move forward. Thank you for making it possible.
Sincerely,
George Q. Daley, MD, PhD
George Q Daley, MD, PhD | Dean of the Faculty of Medicine | Caroline Shields Walker Professor of Medicine 25 Shattuck Street, Boston, MA 02115 | t: (617) 432-1501 | e: George_Daley@hms.harvard.edu
Research at Harvard Medical School
For more than 200 years, discoveries at Harvard Medical School have driven innovations in medicine and the life sciences, leading to groundbreaking treatments for a wide range of illnesses as well as new strategies to address health inequities and rising health care costs. Today, HMS’s community spans more than 12,000 faculty members across the Quad and our 15 affiliated hospitals. HMS scientists unravel disease biology while clinical researchers advance patient care—all propelling medicine forward through collaboration and the relentless exchange of ideas.
Featured Faculty Research
Stuart Orkin
In December 2023, CASGEVY, a treatment for sickle cell disease and transfusion-dependent beta thalassemia, became the first CRISPR-based gene therapy to receive FDA approval. Its journey to that milestone began, many years earlier, in the Orkin lab. Sickle cell disease is the result of a mutation in the gene that makes hemoglobin, the protein in red blood cells that carries oxygen through the blood. Dr. Orkin and his colleagues determined that hemoglobin comes in two forms: a fetal form, which functions normally even in sickle cell patients, and an adult form, which the disease affects. Shortly after birth, the human body shuts down production of fetal hemoglobin, and sickle cell patients begin producing abnormal adult hemoglobin.
Dr. Orkin had the idea of switching the body’s production of fetal hemoglobin back on in sickle cell disease patients. Working with one of his MD-PhD students, Vijay Sankaran (now the Jan Ellen Paradise, MD Professor of Pediatrics at Harvard Medical School, with a lab of his own); patient samples from the National Institutes of Health; and a team in Sardinia, Italy, he identified the gene that suppresses production of fetal hemoglobin: BCL11A. Orkin and Sankaran’s 2008 paper in Science, “Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A,” ushered in a new era of sickle cell disease research.
Five years after that breakthrough, another member of the Orkin lab, Daniel Bauer (like Sankaran, now an HMS professor) identified a DNA sequence in BCL11A that, when removed, drastically reduced the gene’s activity. From there, the Orkin lab’s discoveries moved toward clinical applications. David Altshuler, MD ’94, PhD ’94, had been another of Sankaran’s professors; having moved full-time to Vertex Pharmaceuticals (where he is now Chief Scientific Officer), he sought to capitalize on the Orkin lab’s research. After another decade of work, Vertex made history with the launch of CASGEVY.
Stuart H. Orkin, MD ’72, is the David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School and an HHMI Investigator at Boston Children’s Hospital. Across decades of work, the Orkin lab has defined the molecular basis of human blood disorders and the mechanisms that govern blood cell development.
Stuart Orkin
Arlene Sharpe, MD ’82, PhD ’81, the Kolokotrones University Professor at Harvard University and chair of the Department of Immunology at Harvard Medical School, and Gordon Freeman, PhD ’79, professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, have been married for 47 years. They have been scientific collaborators for just as long, dedicating their careers to investigating the immune system and teasing out the secrets that have made effective cancer immunotherapy possible.
Sharpe & Freeman
Arlene Sharpe & Gordon Freeman
In the early 2000s, Drs. Sharpe and Freeman, alongside other colleagues, discovered that some cancers eluded detection and destruction by the immune system by hijacking an immune pathway called PD-1/PD-L1. They found that by blocking either of the two molecules, PD-1 or PD-L1, or deleting the genetic instructions that lead the body to produce them, they could enhance T-cell immune activity against cancer. In animal models, they were able to restore the body’s ability to find and fight tumors.
Ira Mellman, PhD, then vice president of cancer immunology at the biotechnology company Genentech, took up the task of designing anti-PD-1 and anti-PD-L1 therapies, using Dr. Sharpe’s and Dr. Freeman’s research, that could improve the human immune system’s ability to resist cancer. Mellman’s team led their candidate through clinical trials and eventually brought the drug, now known as Tecentriq, to FDA approval in the United States.
Today, similar drugs—immune checkpoint inhibitors—have greatly expanded and improved oncologists’ arsenals and changed the lives of enormous numbers of cancer patients. Before the widespread availability of such therapies, few patients survived metastatic melanoma for more than two years. In a recent long-term study following up on clinical trials, researchers found that half of patients with advanced melanoma who were treated with checkpoint inhibitors were still alive after 10 years.
Bob Datta
The Datta lab identified a previously unknown class of odor receptor that, when mutated, appears to decrease the risk of Alzheimer’s disease. Having studied these receptors, the team determined that the wild-type version “smells” inflammation and promotes the recruitment of T cells into the brain in the later stages of disease, which accelerates neurodegeneration. The team is currently studying this phenomenon in a mouse model of Alzheimer’s. By knocking out or knocking down the relevant gene (i.e., stopping or decreasing its expression), Dr. Datta and his colleagues can completely prevent late-stage Alzheimer’s symptoms—even in brains already burdened by extensive amyloid plaques.
In another project, Dr. Datta’s team used machine-learning methods to analyze how behavior evolves over an organism’s lifespan. They discovered that mouse behavior embodies an “aging clock”: with just 15 minutes of video, researchers can tell how old that mouse is, give or take two weeks. By analyzing the behavior of a mouse any older than one year, they can accurately predict when it will die, even when this will occur more than a year later. Dr. Datta believes this shows that behavior is a key analytic for determining functional age, an insight with important implications for the use of behavior as a metric for health.
Bob Datta
HMS neurobiology professor Sandeep Robert “Bob” Datta, MD '04, PhD '04, studies how the brain processes information related to smell, which, for the mice neurobiologists work with, is the most important of the five senses. Datta’s lab dissects the basic neural mechanisms that give order and structure to complex natural behaviors, and investigates how olfactory and motor systems influence each other to help animals interpret their environment.
Isaac Ming-Cheng Chiu, AB '02, PhD '09, professor of immunology at HMS, leads a lab focused on the neuroimmune mechanisms underlying pain, host defense, and neurodegeneration.
Isaac Chiu
Isaac Chiu
Recent work by Chiu lab alumnus Dylan Neel (“Gasdermin-E Mediates Mitochondrial Damage in Axons and Neurodegeneration”) formed the basis for some of the Chiu lab’s most promising discoveries in neurodegenerative illness. Dr. Neel studied amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, an invariably fatal motor neuron disease that causes death in most patients within two to five years of diagnosis. His team found that, in the course of the disease, the protein Gasdermin-E starts an inflammatory cascade, opening pores in mitochondria and causing axon degeneration and ultimately neuron death.
By genetically inhibiting Gasdermin-E production, Chiu lab researchers found that they could prevent axon loss in motor neurons derived from ALS patients and ameliorate disease in a mouse model of ALS. In the latter case, the mice lived longer and experienced less motor dysfunction, less motor neuron loss, and reduced neuroinflammation. The lab is presently working on new knockdown methods and studying Gasdermin-E’s role in both human stem cell and mouse models of Alzheimer’s disease. Suppressing Gasdermin-E expression will hopefully prove relevant to the treatment of not just ALS and Alzheimer’s, but also cortical diseases, dementia, and many other neurodegenerative illnesses.
The Chiu lab also continues to study the links between pain, itch, and microbial infection, investigating whether microbes contribute to chronic pain and examining nociception in the skin. Their work with mouse models has been promising: when researchers treat mice with antibiotics, the animals experience less chronic pain. The team is also investigating the mechanism behind chronic pain caused by Lyme disease and how botulinum toxin—which blocks the body’s local response to nerve signals—might treat infection. They also proved for the first time that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, secretes a protease that directly activates sensory neurons, driving itch and causing skin damage.