--- title: "2026-2027 QFASTR" canonical: "/2026-2027-qfastr" published: 2026-10-01 --- # 2026-2027 QFASTR ## Frame ### Quadrangle Fund for Advancing and Seeding Translational Research ###### October 2026 ##### at Harvard Medical School ## Frame October 1, 2026 Dear Phill and Liz, I’m pleased to share an overview of the new Q-FASTR projects for fiscal year 2027, and to thank you once again for your crucial, foundational support of this transformative program. Q-FASTR has grown steadily in impact and reach over the years, becoming one of the world’s foremost pipelines from basic science research to commercialization and clinical impact, and an engine for innovation on the HMS Quad. The projects selected for funding this year promise new treatments for specific illnesses such as type 1 diabetes and pulmonary arterial hypertension, as well as exciting new approaches to some of the most longstanding challenges our profession has sought to address, such as skin damage and pain itself. They represent the best medical science has to offer and exemplify our mission to improve health and well-being for all. In this report, each project is described by its principal investigator, offering a firsthand perspective on its promise and potential. ###### George Q. Daley, MD, PhD Thank you for your generosity, your vision in championing Q-FASTR, and your continued good counsel. I wish you a pleasant fall and hope to see you both soon. Sincerely, George Q. Daley, MD, PhD Dean of the Faculty of Medicine Caroline Shields Walker Professor of Medicine **BMPR2** ## Frame RESTORING BMPR2 FUNCTION #### Validating Novel Therapeutic Targets in Pulmonary Arterial Hypertension Adrian Salic, PhD, Professor of Cell Biology Dick van den Boomen, PhD, Research Associate Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease characterized by pulmonary vascular remodeling and right ventricular heart failure. Current treatments focus on vasodilation and do not directly address the molecular mechanisms driving the disease. Impaired bone morphogenetic protein (BMP) signaling, frequently caused by loss-of-function mutations in the BMPR2 gene, is a major contributor to PAH. Restoring BMP receptor abundance and signaling, therefore, represents a promising disease-modifying strategy. Our research has identified a previously unrecognized pathway that regulates BMPR2 stability and degradation. The objective of this project is to define how this pathway controls receptor abundance and determine whether it can be therapeutically manipulated to restore BMP signaling. We will investigate the underlying molecular mechanisms, develop approaches to stabilize BMPR2, and evaluate their ability to restore signaling in patient-derived PAH cells. This work could establish BMPR2 stabilization as a new therapeutic strategy and lay the foundation for developing treatments targeting a central molecular driver of PAH. Adrian Salic, PhD Dick van den Boomen, PhD **HIV-1** ## Frame HIV-1 DIAGNOSTIC DEVELOPMENT #### Quantitative Field-Deployable Diagnostic Michael Springer, PhD Ra'Mal Harris Michael Springer, PhD, Professor of Systems Biology Ra’Mal Harris, Graduate Student This pilot project addresses the critical lack of a simple, quantitative at-home HIV-1 viral load test. Existing lateral flow and isothermal assays are either insufficiently sensitive or overly equipment-dependent for decentralized HIV monitoring, thereby limiting the implementation of care based on the “undetectable = untransmittable” strategy. We will develop a closed-tube, LAMP-based assay that generates stable single-stranded DNA (ssDNA) and couples it to highly specific, sequence-encoded detection chemistries. First, we’ll test two novel modifications to generate ssDNA products in an HIV-1 LAMP assay. Next, we’ll systematically compare probe-based methods to detect this ssDNA in a one-pot reaction. Finally, we’ll implement a quantitative competition framework using an internal double-stranded DNA reference to enable robust viral load measurement despite nonspecific amplification, with readout via nanoparticle-mediated color changes. Together, these studies will establish the feasibility of a future low-cost, at-home molecular HIV-1 viral load assay and identify its optimal components. **Skin Prevention** ## Frame SKIN CANCER PREVENTION #### Melanocortin-1 Receptor Agonist for Treating Xeroderma Pigmentosum and Others at High Risk of Skin Cancers Andrew Kruse, PhD Jeffrey Smith, MD, PhD Andrew Kruse, PhD, Professor of Biological Chemistry and Molecular Pharmacology Jeffrey Smith, MD, PhD, Assistant Professor of Dermatology, Brigham and Women's Hospital Nora Gravgaard, Research Associate Benjamin Grupp, Postdoctoral Fellow The melanocortin-1 receptor (MC1R) plays a key role in regulating melanin production, which determines skin pigmentation. Peptide agonists targeting MC1R enhance melanin production, leading to increased pigmentation; the FDA has approved one such molecule to treat skin damage caused by porphyria. Unfortunately, the clinical utility of current MC1R peptides is significantly limited by their rapid clearance and cross-reactivity with other melanocortin receptors. Given the role of skin pigmentation in various diseases and in skin cancer prevention, a selective and potent MC1R agonist could have multiple clinical uses, significantly improving the current standard of care and expanding its indications. We have created a humanized MC1R agonist antibody with high affinity and selectivity for MC1R that darkens human skin. Here, we propose to advance an MC1R agonist antibody biologic with a validated, de-risked mechanism of action from an experimental tool to a development candidate ready for out-licensing to treat the orphan disease xeroderma pigmentosum. The overall objective of this proposal is to optimize and de-risk our lead MC1R agonist antibody candidate, JSS002.2, and test it in animal models. **Skin Regeneration** ## Frame SCARLESS SKIN REGENERATION #### Therapeutic Strategies for Scarless Skin Regeneration After Injury Ya-Chieh Hsu, PhD Rebecca Freeman Arianna Donas, PhD Ya-Chieh Hsu, PhD, Professor of Stem Cell and Regenerative Biology Rebecca Freeman, Graduate Student Arianna Donas, Research Assistant More than 100 million people in the developed world alone develop scars each year, and more than six million in the United States suffer from chronic, non-healing wounds. Skin is a complex, multi-lineage organ that enables protection, sensation, and thermoregulation, yet after injury, healing is limited to epidermal closure, and other skin cell types are replaced by fibrotic scar tissue. As a result, healed skin remains structurally and functionally impaired. Current therapies focus on infection control and wound closure but do not prevent scarring or restore the cellular diversity required for fully functional skin. A therapy that converts fibrotic repair into true organ-level regeneration represents a major unmet clinical need. Embryonic skin, unlike postnatal skin, can fully regenerate after full-thickness injury. By comparing embryonic and postnatal wound healing, we identified the protein CXCL12, produced by postnatal wound fibroblasts, as a key inhibitor of regeneration. Fibroblast-specific deletion of the CXCL12 gene restores multi-lineage regeneration, establishing CXCL12 as a promising therapeutic target. Unlike other scar-reducing strategies, which primarily limit fibrosis, targeting this pathway has the potential to both reduce fibrosis and restore multi-lineage regeneration. The objective of this proposal is to develop a clinically actionable strategy that leverages the biology of CXCL12 to enable regenerative wound healing. We will systematically evaluate complementary therapeutic approaches and compare their efficacy, safety, and translational feasibility in preclinical models. These studies will identify the approach with the greatest translational potential and establish key parameters for dosing, delivery, and biological response. **Chronic Pain** ## Frame CHRONIC PAIN THERAPIES #### Monoclonal Antibodies for Precision Delivery of Analgesic Therapeutics to Peripheral Nervous System Neurons David Ginty, PhD David Ginty, PhD, Edward R. and Anne G. Lefler Professor of Neurobiology Jing Peng, PhD, Research Associate Siyi (Tracy) Huang, PhD, Venture Fellow Jing Peng, PhD Peripheral neuropathy affects 15–20 million Americans, often manifesting as debilitating chronic pain and driving over $10 billion in annual health care costs. Existing therapies offer limited efficacy and are constrained by systemic side effects and risks of misuse or addiction. These problems underscore a critical unmet need for precision neurotherapies that target the nociceptive circuit, the neural pathway that detects signals of tissue damage and reports them as pain. This proposal introduces a first-in-class platform that harnesses a nociceptor-enriched target protein as a selective delivery address. By developing monoclonal antibodies and, subsequently, antibody–drug conjugates (ADC) and antibody–oligonucleotide conjugates (AOC) targeting this nociceptor protein, this strategy enables targeted delivery of potent payloads directly to pain-sensing neurons. This approach aims to achieve durable modulation of nociceptor function while minimizing systemic exposure. The primary objectives are to generate and validate high-affinity, extracellular-binding, target protein–specific antibodies suitable for conjugation, and to characterize their internalization properties to guide optimal payload/modality selection. Success will establish a scalable, patentable platform with broad applicability across chronic pain indications, enabling access to previously undruggable intracellular targets and positioning this technology for meaningful clinical and commercial impact. Tracy Huang, PhD **Respiratory** ## Frame RESPIRATORY INFECTION REPAIR Ruth Franklin, PhD Daisy Hoagland, PhD #### Development of a Novel Therapeutic to Accelerate Epithelial Repair Following Viral Respiratory Infection Ruth Franklin, PhD, Associate Professor of Stem Cell and Regenerative Biology Daisy Hoagland, PhD, Research Fellow Stephen Liberles, PhD, Professor of Cell Biology Michael Schappe, PhD, Assistant Professor of Molecular & Integrative Physiology, University of Illinois Urbana-Champaign Stephen Liberles, PhD Michael Schappe, PhD Respiratory infections impose a significant global health burden, and the emergence of novel viruses, such as SARS-CoV-2, further underscores the urgent need for new therapeutic strategies. Current treatments focus on eliminating pathogens, boosting immunity, or suppressing inflammation; approaches to mitigate infection-induced tissue damage remain underexplored. We propose harnessing lung epithelial repair as a novel therapeutic avenue to improve outcomes in patients with severe respiratory infections and associated lung pathology, particularly when standard treatments, such as antivirals, are no longer effective. Using mouse models of viral-induced lung damage, we will evaluate the therapeutic potential of administering a pro-repair factor to mitigate lung injury and promote recovery following severe viral respiratory infections. **Diabetes** ## Frame TYPE 1 DIABETES REVERSAL #### Induction of Autoantigen-Specific Tolerance to Reverse Type 1 Diabetes Amy Wagers, PhD Amy Wagers, PhD, Forst Family Professor of Stem Cell and Regenerative Biology Alborz Karimzadehfard, PhD, Postdoctoral Fellow Gabi Quickstad, PhD, Postdoctoral Fellow Thomas Serwold, PhD, Investigator, Joslin Diabetes Center Millions of people around the world live with type 1 diabetes (T1D), a chronic, incurable autoimmune condition that produces significant acute and long-term health complications. T1D is caused by the destruction of insulin-producing beta cells by immune cells that escape the body’s normal mechanisms for tolerance induction. Our research seeks to develop novel interventions that can effectively eliminate or inactivate this immune cell–mediated autoimmune attack on pancreatic beta cells, thereby establishing a new, curative therapy for T1D. Our experimental approach engages the body’s natural pathways to induce specific tolerance and has shown promise in preventing the initiation of T1D in a mouse model of beta-cell autoimmunity. We will test whether our strategy can additionally halt ongoing beta-cell destruction and rescue diabetes pathology at later stages of the disease—after the onset of immune infiltration of the pancreas and potentially even after the emergence of overt clinical symptoms. Successful completion of this work could validate a new, targeted approach to reestablish and sustain immune tolerance as an effective clinical therapy for T1D and autoimmunity more broadly. Alborz Karimzadehfard, PhD Gabi Quickstad, PhD Thomas Serwold, PhD **Radioprotection** ## Frame RADIOPROTECTION THERAPY #### Tuning p53-Dependent Cell #### Fate for Radioprotection #### and Mitigation This project aims to develop a small molecule that “tunes” p53-dependent cell-fate decisions following radiation exposure to favor tissue preservation over cell death. By modulating the signaling dynamics of the tumor-suppressor protein p53, the therapy is designed to prevent or mitigate the lethal tissue injury that underlies acute radiation syndrome in otherwise healthy individuals. Over two years, the team will generate a translational package that includes pharmacokinetics, pharmacodynamics, specificity, and early safety data, along with functional studies in human and mouse hematopoietic systems and human intestinal organoids. These efforts will be complemented by in vivo efficacy studies in mouse models of radiation injury to support the advancement of this agent as a single-agent medical countermeasure suitable for stockpiling and rapid deployment. Galit Lahav, PhD Galit Lahav, PhD, Novartis Professor of Systems Biology **Hair Regeneration** ## Frame HAIR REGENERATION THERAPEUTICS Ya-Chieh Hsu, PhD Jingyu Peng Arianna Donas, PhD #### Novel Therapies for Hair Loss Ya-Chieh Hsu, PhD, Professor of Stem Cell and Regenerative Biology Jingyu Peng, Graduate Student Arianna Donas, Research Assistant Hair loss affects hundreds of millions worldwide and can be androgenetic, stress-associated, or age-related. Current treatments are limited to oral dihydrotestosterone (DHT) inhibitors and topical minoxidil. DHT inhibitors require continuous use, have systemic side effects, and are not approved for use in women. Minoxidil promotes vasodilation but has limited efficacy and does not restore stem cell function. There is a clear unmet need for therapies that safely and effectively reactivate hair follicle stem cells (HFSCs) to enable hair growth across a wide range of conditions. Our studies have identified a class of small-molecule compounds that potently promote HFSC activation and hair regeneration. In mouse models, a single treatment induces rapid and robust stem cell activation and hair growth, with efficacy exceeding all HFSC-targeting approaches evaluated to date. These compounds have favorable drug-like properties and represent a promising therapeutic strategy for directly promoting endogenous hair regeneration. We will rigorously assess the efficacy and safety profile of these compounds, including local versus systemic effects, and test their ability to promote human hair follicle regeneration in culture and in xenograft models using human scalp skin transplanted onto immunodeficient mice. These studies will establish the compounds’ therapeutic potential and evaluate their relevance to human biology. Together, this work will advance a new class of regenerative therapeutics toward more effective, localized, and broadly applicable treatments for hair loss. ## Frame ###### Office of Alumni Affairs and Development ###### 25 Shattuck Street Boston, MA 02115