Q-FASTR Impact 2026-2027

Since 2014, the Quadrangle Fund for Advancing and Seeding Translational Research (Q-FASTR) has accelerated early-stage research with potential for commercialization and, ultimately, the promise of improving people’s health. Since its inception, Q-FASTR has served as a critical nexus between basic science discoveries and innovative therapeutic possibilities. By providing funding, skills development, and project management, Q-FASTR removes obstacles to developing early-stage discoveries and creates new entry points for nascent technologies poised for commercialization. Q-FASTR buoys Harvard Medical School’s efforts to foster a research culture centered on therapeutic invention. Since the program’s launch, more than half of the laboratories on the Quad have sought Q-FASTR funding, indicating a growing and widespread interest in translation. By supporting HMS faculty with funding, resources, and partnerships, Q-FASTR has also laid the foundation for the Therapeutics Initiative, enabling researchers to demonstrate the merit and feasibility of their innovative ideas.

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.

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.

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.

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.

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.

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.

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.

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.

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.

at Harvard Medical School

Quadrangle Fund for Advancing and Seeding Translational Research

October 2026

Q-FASTR by the Numbers

Validating Novel Therapeutic Targets in Pulmonary Arterial Hypertension

Quantitative Field-Deployable Diagnostic

Melanocortin-1 Receptor Agonist for Treating Xeroderma Pigmentosum and Others at High Risk of Skin Cancers

Therapeutic Strategies for Scarless Skin Regeneration After Injury

Monoclonal Antibodies for Precision Delivery of Analgesic Therapeutics to Peripheral Nervous System Neurons

Development of a Novel Therapeutic to Accelerate Epithelial Repair Following Viral Respiratory Infection

Induction of Autoantigen-Specific Tolerance to Reverse Type 1 Diabetes

Tuning p53-Dependent Cell

Fate for Radioprotection

and Mitigation

Novel Therapies for Hair Loss

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