Challenge-Driven Research Programs
The Longfellow Project
Office of the Scientific Director
125 Nashua St.
Boston,
MA
02114
A Promising New Approach to Tackling Pressing Medical Issues
The Longfellow Project’s Challenge-Driven Research Programs take a comprehensive approach to identifying and designing solutions to important healthcare problems. The team has instituted a new model of collaboration that leverages fundamental and translational research, clinical care, and access to high-quality patient samples, enabling bench-to-bedside-to-bench translation while considering market drivers.
To establish these programs, the Strategic Alliances team in the Office of the Scientific Director worked closely with investigators and leadership across Massachusetts General Hospital and with external advisors from the pharma, biotech, and venture communities, including members of the Research Institute Advisory Council.
The aim is to provide funding for each program to support early-stage, proof-of-concept research that will leverage further funding and industry agreements.
Robert Tepper, MDWe have an incredible biomedical ecosystem here in Boston, it's probably unique in the world. It has some of the best hospitals in the world, some of the best medical research. The need for multiple groups—basic scientists, physicians, business leaders, people—to work together to come up with solutions has never been greater.
Partner, Third Rock Ventures
Programs
To date, eight Challenge-Driven Research Programs composed of 261 investigators from 21 Mass General departments and centers have come together with key industry partners to focus on new diagnostics and treatments for health issues that affect vast numbers of patients:
Antimicrobial Resistance
Bacterial-resistant infections | All bacterial infections
73 Lead Scientists
Collaborating Departments and Centers: Center for Computational and Integrative Biology • Department of Dermatology • Department of Medicine • Department of Molecular Biology • Department of Pediatrics & Pediatric Surgery • Department of Obstetrics & Gynecology • Department of Surgery • Emergency Medicine • Wellman Center for Photomedicine
Key Challenge: How can antibiotics be used effectively and responsibly to treat bacterial infections without increasing antibiotic resistance?
Relevant Issues: By 2050, it is estimated that the number of deaths due to antibiotic resistant bacterial infections will be ten times higher than deaths due to cancer. We are working to develop new diagnostic tools to analyze the genome of the infectious bacteria, new drugs to treat specific infections, and new models of stewardship to ensure safe and directed antibiotic use.
Cancer Immunotherapy
Multiple cancers | Malignant and benign tumors
33 Lead Scientists
Collaborating Departments and Centers: Center for Systems Biology • Mass General Cancer Center • Department of Dermatology • Department of Medicine • Department of Otolaryngology • Department of Pathology • Department of Radiation Oncology • Department of Surgery
Key Challenges: Why do some people respond to immunotherapies while others do not?
How can we prevent toxic responses to immunotherapy treatments that often develop over time?
Relevant Issues: Tumors are complex masses of cancerous and non-cancerous cells, including cells of the immune system. Immunotherapy boosts the immune cells’ ability to kill cancerous cells and has shown great potential in treating a range of tumor types. But response to treatment varies widely between patients and over time. Understanding the immune biology of tumors will help realize the promise of immunotherapy to turn cancer into a manageable chronic disease.
Cardiometabolics
Heart failure | Arrhythmia | Vascular disease | Metabolic disorders
23 Lead Scientists
Collaborating departments and centers: Center for Systems Biology • Department of Medicine • Department of Pathology • Department of Radiology • Department of Surgery • Martinos Center for Biomedical Imaging • Wellman Center for Photomedicine
Key challenge: How do we advance from treatment to cure?
Relevant issues:
- The epidemic of cardiovascular diseases is related to multiple factors, including higher survival rates for heart disease and stroke; increasing our understanding of why certain people survive cardiac events or heart conditions will play a pivotal role in addressing and eradicating cardiometabolic diseases.
- Revealing the biologic mechanisms of cardiometabolic disease will result in a clearer understanding of the biologic underpinnings of patients’ conditions and guide the application of new, effective treatments.
- Identifying the relationship between cardiovascular diseases and other mechanisms like inflammation will guide biomarkers and target discovery.
Cardiometabolic diseases affect millions of people and are a leading cause of death worldwide. Mass General treats tens of thousands of patients across cardiology, the Mass General Corrigan Minehan Heart Center and many other departments and centers, giving us a critical advantage in tackling these diseases.
Epigenetics
Nearly all forms of cancer and tumors | Dementia and multiple neurological diseases
13 lead scientists
Collaborating Departments and Centers: Department of Dermatology • Department of Medicine • Department of Molecular Biology • Department of Neurology • Department of Pathology • Mass General Cancer Center
Key Challenge: How do changes in when, whether and how often the information stored in a gene is used alter the activity of a cell and lead to disease?
Relevant Issues: Epigenetics involves the properties of gene regulation (whether and when a gene’s instructions are used) and gene activity (the frequency that a gene’s instructions are used). Epigenetics add a dynamic layer of control to cell activity and changes in these properties can lead to disease. We are working to develop a comprehensive understanding of gene regulation and activity which will provide a more complete picture of the root causes of disease and inform the development of new therapeutics to maintain healthy cell activity.
Microbiome
Obesity | Reproductive Health | Multiple Other Diseases and Disorders
19 Lead Scientists
Collaborating Departments and Centers: Department of Medicine • Department of Obstetrics & Gynecology • Department of Pediatrics & Pediatric Surgery • Department of Surgery • Wellman Center for Photomedicine • Center for Systems Biology
Key Challenge: What role does the human microbiome play in promoting healthy development, maintaining healthy physiology and driving disease?
Relevant Issues: The human body contains at least as many microbial cells as its own cells. These microbial cells form a second genome in each individual. Studying this second genome has advanced our understanding of how the microbiome promotes human health or disease. For example, changes to the composition of microbes in the gut have been linked to chronic inflammatory and neurodegenerative diseases. Our focus is on preventative and therapeutic treatment options that support healthy microbiome development and function.
Neuroinflammation in Neurodegeneration
Alzheimer’s disease | Amyotrophic lateral sclerosis (ALS) | Multiple sclerosis | Other neurogenerative diseases
25 Lead Scientists
Collaborating Departments and Centers: Department of Medicine • Department of Dermatology • Department of Neurology • Department of Radiology • Department of Surgery • Wellman Center for Photomedicine • Martinos Center for Biomedical Imaging
Key Challenges: Is neuroinflammation a therapeutic target across neurodegenerative diseases? Would targeting neuroinflammation enable early detection and treatment before symptom onset?
Relevant Issues: In recent years, clinical observations and lab-based research have linked neuroinflammation to neurodegeneration and to clinical symptoms. These findings suggest that the genes regulating innate immunity could serve as targets for preventing and treating neurodegenerative diseases such as Alzheimer’s and potentially help patients before symptoms develop.
Rare Diseases
Over 30 rare disease being treated and studied at Mass General
52 Lead Scientists
Collaborating Departments and Centers: Center for Genomic Medicine • Center for Systems Biology • Department of Medicine • Department of Molecular Biology • Department of Neurology • Department of Pathology • Department of Pediatrics & Pediatric Surgery • Department of Radiation Oncology • Department of Radiology • Department of Surgery • Martinos Center for Biomedical Imaging • Physical Medicine and Rehabilitation • Wellman Center for Photomedicine • Mass Eye and Ear: Departments of Otolaryngology; Department of Ophthalmology; Schepens Eye Research Institute
Key Challenges: Is it possible to create a systematic, patient-centered approach to understand the biology underlying each rare disease? Can we develop mechanism-based treatments that benefit patients and family members at-risk for the same rare disease?
Relevant Issues: This program will speed diagnosis and development of patient genotype-based treatments for 30 rare diseases being treated and studied at Mass General. It leverages the advanced technology tools available at Mass General, such as the therapeutic delivery of DNA sequences into patients’ cells (gene therapy); genetic engineering in which DNA can be deleted, modified or replaced to prevent or cure diseases (gene editing); and other gene-related approaches to disease treatment, prevention and screening.
Sleep
Autism spectrum disorder | Cardiovascular and metabolic disorders | Schizophrenia | Neurodegenerative diseases | Multiple other health issues
23 Lead Scientists
Collaborating Departments and Centers: Center for Systems Biology • Center for Genomic Medicine • Department of Anesthesia, Critical Care & Pain Medicine • Department of Dermatology • Department of Medicine • Department of Obstetrics & Gynecology • Department of Pediatrics & Pediatric Surgery • Department of Surgery • Wellman Center for Photomedicine
Key Challenge: How do sleep and circadian rhythm disruptions or disorders drive disease, and vice versa?
Relevant Issues: Sleep is controlled by circadian rhythms and is essential for human health — during sleep our bodies clear toxins from the brain, undergo physical restoration, process information and consolidate memories, regulate mood and strengthen the immune system. Sleep and circadian rhythms disruptions (e.g., shift work, newborn care) and disorders (e.g. insomnia, sleep apnea) impact overall health by decreasing wakefulness, performance and productivity; increasing stress and anxiety and driving a wide range of diseases. Understanding how sleep impacts disease, and vice versa, will allow us to develop new diagnostics and treatments to address a vast array of diseases and improve overall health.
Results
The programs have already had a dramatic impact on moving science forward. As new discoveries are made, scientists can seek feedback from industry collaborators on factors that could advance or inhibit the ability to develop novel approaches and deliver them to market to help patients.
These efforts have resulted in extensive meetings with 14 pharmaceutical and biotech companies, with one collaboration agreement executed and launched and other discussions in progress.
The Longfellow Project
The Longfellow Project bridges the divide between academic research and industry-based R&D, bringing together leading biomedical researchers and physician-scientists at Mass General to work with one another and with their peers in industry.