Ben Ebert is a hematologist and oncologist whose research focuses on cancers and other disorders that affect the production of red blood cells. He also leads the leukemia program at the Dana-Farber/Harvard Cancer Center.
Since September 2014, BroadIgnite has supported a wide array of innovative projects to drive biology forward and revolutionize our understanding of disease. Learn more about our awardees and their funded projects below.
Ben Ebert is a hematologist and oncologist whose research focuses on cancers and other disorders that affect the production of red blood cells. He also leads the leukemia program at the Dana-Farber/Harvard Cancer Center.
Laboratory models of leukemia often don’t reflect the genetic reality of patients’ cancers. Ben is tackling this challenge by using the CRISPR genome-editing tool to develop new models of drug-resistant childhood leukemias with more realistic mutations—including some identified in his lab. These models can be used to search for new treatments that can kill the drug-resistant cancer cells. This project will provide researchers with a steady and reliable source of leukemia models to advance our understanding of blood cancers and test new experimental therapies.
Ebert and his team have created several models and used them to test how different mutations change how the blood cancers respond to a specific cancer drug.
Nick Haining is a pediatric oncologist who studies cancer immunology—harnessing a patient’s immune system to attack tumors. Nick also sees patients at the Dana-Farber Cancer Institute.
Recent developments in cancer immunotherapy hold great promise, but so far only a tiny fraction of patients respond to the current drugs. Nick hopes to lay the groundwork for identifying new therapeutic targets by understanding the underlying biology of the interactions between cancer and the immune system. He’s using his BroadIgnite funds to systematically and comprehensively identify the genetic mutations and pathways that enable tumors to elude our immune defense.
Nick’s laboratory has built the tools necessary to tackle this project—mouse cancer cell lines for melanoma, lung cancer, and colon cancer, using the CRISPR genome-editing tool. His team is now working closely with the Broad’s Genetic Perturbation Platform to scan the genome to identify the genes involved in cancer therapy resistance, and probe some of these promising genes to identify new therapies.
Daniel MacArthur is a geneticist who pulls useful information out of genetic “big data.” He is also an assistant professor at Harvard Medical School.
As a BroadIgnite awardee, Daniel is using his funds to launch an initiative to provide definitive diagnoses for 20 patients suffering from rare muscle diseases using a method developed at the Broad. By sequencing the patients’ expressed genes, he’s working to identify the exact genetic cause of these severe diseases.
Using the latest Broad technology, the MacArthur lab has analyzed the expressed genes from 37 patients with severe muscle disease. As a result, the lab has successfully diagnosed 15 patients with rare disorders, and continues to crunch the data for the remaining participants. For three of these patients’ families, clinical collaborators have designed prenatal tests to enable them to have healthy additional children.
Anthony Philippakis is a physician, geneticist, and data scientist. He is also a cardiologist at Brigham and Women’s Hospital, where he cares for patients with rare genetic cardiovascular diseases.
BroadIgnite funding is supporting Anthony’s efforts to launch a “Genomic Matchmaker” database. This revolutionary database will allow clinicians and researchers to rapidly scan vast catalogs of genomic data to find other samples with the same genetic changes—advancing biomedical research and guiding clinical decisions.
BroadIgnite support has seeded further funding of the “genomic matchmaker” devised by Anthony and his colleagues. Thanks to BroadIgnite funds, he has recruited a key staff member to identify suitable patient cohorts and manage the portal’s large datasets, and his team is now refining and extending existing software.
Eliezer Van Allen is a cancer researcher who uses genomics to guide treatment decisions in genitourinary (prostate, kidney, testicular, and bladder) cancers. He is also a practicing oncologist at Dana-Farber/Partners Cancer Care.
Eli is using BroadIgnite funding to study exceptional responders—cancer patients who respond extremely well to new immunotherapies.
Eli and his team have sequenced the expressed genes of five exceptional responders and three of the resistant tumors from these patients. That allowed them to identify a new gene candidate that mediates the response to a novel cancer immunotherapeutic. Eli is now analyzing the data to identify other genes that could play such a role, especially in rare cancers like sarcoma.
Eric Minikel and Sonia Vallabh are Ph.D. students in Stuart Schreiber's laboratory at the Broad Institute. In 2010, Sonia’s mother abruptly developed and died of prion disease— a rapidly progressive and fatal neurodegenerative disorder caused by the spread of misfolded proteins in the brain. The following year, Sonia learned she had the same mutation that caused her mother’s disease. Thus, Sonia and her husband Eric left their career in consulting to begin studying biology, with the long-term goal of designing small molecule therapeutics for prion diseases.
Eric and Sonia are developing methods and models to study prions, find and test new therapeutics, and identify ways to track the progress of the disease.
With their BroadIgnite funds, they have set up a dedicated room at the Broad with all the tools necessary to establish RT-QuIC, a new assay, as a tool for drug discovery. They are now isolating pure prion protein from cells to use in their experiments.
Alex Shalek is a chemical biologist who uses nanotechnology techniques to understand how cells work together in health and disease. He is the Hermann L.F. von Helmholtz Career Development Professor at the Harvard-MIT Program in Health Sciences and Technology (HST) and an assistant professor of chemistry at MIT, where he is a core member of the Institute for Medical Engineering and Science. He is also an associate member of the Ragon Institute of MGH, MIT and Harvard.
BroadIgnite funding is supporting the Shalek lab’s efforts to use cutting-edge single-cell genomic assays to study HIV. They’re studying how a rare population of HIV+ individuals, known as elite controllers, prevents the spread and growth of the virus in their bodies without treatment. The award has enabled the lab to travel to Durban, South Africa to follow up on initial findings with collaborators at the Kwazulu-Natal Research Institute for Tuberculosis and HIV.
Sara Jones is a postdoctoral fellow in Feng Zhang's lab at the Broad Institute. Her research focuses on identifying and developing novel strategies for gene editing through the study of organisms that aren’t usually studied in the lab.
BroadIgnite funding is supporting Sara’s efforts to adapt the clever genetic strategies of “pond scum” for therapeutic use. She studies a pond-dwelling microorganism that shatters its DNA into hundreds of thousands of pieces, which it must rearrange and reassemble to survive. By understanding how such complex genome architectures can be sustained in nature, she hopes to build a new platform for gene therapy in mammalian cells.
Nikhil Wagle is a medical oncologist who studies cancer genomics and precision cancer medicine. He characterizes the genomes of patient tumor samples to better understand the molecular roots of cancer and drug resistance and to identify mutations that can be targeted with available treatments.
BroadIgnite support has propelled Wagle's Metastatic Breast Cancer (MBC) Project, an initiative to recruit people across the country with metastatic breast cancer to participate in research. The funding has allowed him to analyze some of these samples, with the aim of understanding the differences in tumors that arise in younger versus older patients.
Moran Yassour is investigating how different methods of childbirth affect children’s gut microbiomes.
The bacteria in a baby’s gut can differ radically, depending on how the baby was delivered. But what bacteria are impacted, and why? BroadIgnite is funding Moran’s research into this very question, through a study at Massachusetts General Hospital.
Roby Bhattacharyya is an attending physician in infectious diseases at Massachusetts General Hospital and a postdoctoral researcher in Deb Hung's lab studying antibiotic resistance. He seeks to understand how bacteria adapt to the most powerful antibiotics and design rapid methods for detecting resistance.
BroadIgnite funds will allow Roby to develop and test a rapid diagnostic for meningitis that can identify the responsible pathogen from the cerebrospinal fluid of patients. Bacteria, viruses, or fungi can all cause meningitis, but it can take up to a week to identify the source of the infection. In the meantime, doctors have to make an educated guess—and may end up prescribing antibiotics that don’t actually target the disease, but can instead contribute to antibiotic resistance. Roby seeks to shorten the time to diagnosis by developing an RNA-based assay that would identify the source pathogen by its expressed genes. Unlike current tests, it would work for any variety of meningitis.
Siddhartha Jaiswal is an attending pathologist at Massachusetts General Hospital and a postdoctoral fellow in Ben Ebert’s lab at the Broad Institute studying age-related diseases. His research is focused on the relationship between genetic mutations, cell biology, and aging.
BroadIgnite funding will allow Sidd to analyze the DNA of people with Alzheimer’s to look for age-related genetic mutations that might play a role in the disease. In previous research, Sidd has shown that when age-related mutations occur in blood cells, they can lead to blood cancer. Strikingly, he found that the same set of mutations is also implicated in cardiovascular diseases such as heart attack and stroke. That suggests that these mutations could change how some blood cells function—and also that a shared mechanism underlies diseases of aging like cancer, cardiovascular disease, and dementia. Based on these insights, his BroadIgnite-funded project will determine whether these mutations are also at play in Alzheimer’s; if confirmed, this could eventually lead to powerful new therapeutic avenues in diseases of aging.
Anna Greka, an institute member of the Broad Institute of MIT and Harvard, is a practicing nephrologist and scientist who studies the basic molecular mechanisms of kidney disease in order to eventually develop targeted therapies. She is also an assistant professor at Harvard Medical School and an associate physician in the Renal Division at Brigham and Women’s Hospital.
Genetic kidney diseases are rare but devastating, with extremely limited treatment options. Because there are so few patients, each one can provide clues that can help improve therapy for all sufferers. Anna has identified a kidney disease patient who responds exceptionally well to a particular drug, and with BroadIgnite support, she’ll identify similar patients in order to understand why the drug is effective for them. Those results could improve the lives of many patients—from those with rare, genetic kidney diseases to the millions who have diabetic kidney disease.
Alex Bloemendal is a computational scientist at the Broad Institute of MIT and Harvard and at the Analytic and Translational Genetics Unit of Massachusetts General Hospital. As a member of Broad institute member Ben Neale’s team, Bloemendal builds computational infrastructure to enable biologists to harness “big data” and analyze the genetics of disease.
With BroadIgnite funding, Alex plans to build a new open-source computational tool to expedite diagnosis of a wide variety of diseases.
Viktor Adalsteinsson runs the Cancer Program’s blood biopsy team—a group of scientists, engineers, oncologists, and computational biologists that develops technologies to monitor the progression of cancer and other diseases through a simple blood draw.
BroadIgnite support will accelerate the team’s pioneering efforts to scan the free-floating DNA in blood for signs of cancer and other diseases. The funding will also support the development of high-powered cellular analysis technology, which can yield insights on the cell types commonly damaged during these diseases.
Elinor Karlsson is the director of the Broad’s vertebrate genomics group. She studies dog genetics as a window into the pathways involved in psychiatric and neurodegenerative diseases shared by people and pooches, including autism spectrum disorders (ASD).
With BroadIgnite funding, Elinor’s team will launch an investigation into ASD by collecting behavioral and genetic data on 100 dog-wolf hybrids. Why the hybrids? Compared to dogs, wolves make less eye contact, don’t bond easily with other species, and are sensitive to novelty—behaviors that people with autism often display. Elinor believes that understanding the genes that are different between dogs and wolves will provide important clues about ASD in humans.
Daniel Neafsey is the associate director of the Broad’s Genomic Center for Infectious Diseases. Dan is an expert in mosquitoes and their role in transmitting some of the world’s deadliest diseases, such as malaria and dengue. By unraveling mosquito biology, Dan hopes to learn which drugs, insecticides, and vaccines are likely to work—and why.
BroadIgnite funds will help Dan tackle another mosquito-borne threat: Zika. He’s developing a new way to track mosquitoes in the wild by introducing short, synthetic genetic markers—DNA ‘barcodes’—into larval and adult mosquitoes. By releasing and then recapturing these barcoded bugs, Dan will learn a wealth of information, including mosquito lifespan, population size, and which pest-control measures actually work.
Ashlee Earl wants to understand how lethal, drug-resistant bacteria flourish and spread, with the goal of finding novel intervention strategies.
BroadIgnite support will jumpstart her efforts to thwart the deadly drug-resistant bacteria called carbapenem-resistant Enterobacteriaceae (CRE). Her studies have shown that CRE are more diverse than previously thought—and that this diversity helps them spread rapidly in hospital settings. Ashlee’s team aims to learn more about the genetic diversity of CRE, with the goal of finding therapies that can target the genes and pathways fueling drug resistance.
Amit Khera hopes to prevent heart attacks by understanding the genetic mutations behind cardiovascular disease.
What genetic mutations drive the risk of cardiovascular disease? Amit wants to find out. His research focuses on the clinical interpretations of genetic risk, the smartest ways to communicate genetic risk to patients, and how doctors and patients can modify genetic risk through medicine or lifestyle changes.
Evan Macosko is a physician-scientist who wants to decode mental illness by using novel, high-throughput techniques to analyze brain cells.
An astonishingly diverse and complex collection of cell types populates the human brain—making it difficult to study, especially when you’re trying to learn how cells malfunction in complicated disorders like schizophrenia and autism. Evan and his team will develop new technologies to identify these cells and understand how they contribute to disease.
Mariella Filbin wants to identify genetic dependencies—mutations that the tumors need to survive—in pediatric brain cancers, with the aim of finding potential therapies.
Most children with diffuse intrinsic pontine glioma (DIPG), a pediatric brain tumor that grows rapidly and has no treatment, die within 12 months of their initial diagnosis. With BroadIgnite funding, Mariella will expand the exciting findings she’s recently made about DIPG, describing cancer stem cells and more mature cancer cells in DIPG for the first time, and potentially uncovering therapeutic leads.
Oliver Jonas develops microdevices that diagnose, probe, and treat live tissues within their native environment.
Typically the microdevice—which is smaller than a rice grain—is implanted via biopsy needle into a tumor, where it provides small doses of 30 different chemotherapies and measures the patient’s response to each. The device remains implanted for 24 hours. Then it’s retrieved with the surrounding tissue, which researchers analyze to learn if the therapies were effective. BroadIgnite will support Oliver’s exploration of whether this technique can also work in the human brain, gauging the effectiveness of drugs for neurodegenerative and neuropsychiatric diseases.
Samantha Riesenfeld is interested in using advanced statistical methods from data science to understand food allergy.
Food allergies endanger more than 220 million people worldwide, two-thirds of whom are children. Yet we still barely understand the biology behind these potentially life-threatening reactions to food. We do know that it is related to the interplay between the immune system and epithelial tissue. BroadIgnite funding will help Sam use statistical machine learning approaches to test an unconventional but potentially revolutionary hypothesis: that our nervous system mediates the immune system’s response.
Andrés Colubri is a computational researcher, visual artist, and designer. He develops new tools that integrate statistics and user-friendly visuals and interfaces to help improve our ability to fight emerging outbreaks.
Lassa fever infects 300,000 people a year in West Africa, causing as many as 5,000 deaths. Andrés is developing new tools that help doctors securely share patient data in real time to better track—and ultimately stop—outbreaks of this deadly disease.
Beryl Cummings is a graduate student specializing in cutting-edge genomic technologies.
Rare diseases cause enormous suffering, especially among the youngest patients, and diagnoses can take years. This means that patients and families often have to suffer through long periods of pain and uncertainty. Beryl will use a technology called RNA-sequencing, which analyzes genes expressed across tissues, to determine if it can help physicians provide rapid, accurate diagnoses to patients and their families.
Steven Lubitz is a cardiologist at Massachusetts General Hospital who specializes in arrhythmias.
Atrial fibrillation (AFib), an irregular and often rapid heart rate, affects more than 5 million people in the U.S.; if left untreated, it can triple the risk of stroke. Steven will develop a machine-learning approach to track and analyze genomic data for AFib—both known variants associated with AFib and new variants identified through our research. Our aim is to improve our ability to detect this form of heart arrhythmia.
Zuzana Tothova is a medical oncologist at the Dana-Farber Cancer Institute. Her research focuses on blood cancers, a group of cancers including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
MDS affects 30,000 new people each year in the U.S., and its long-term survival rate is less than 5 percent. About 11 percent of MDS patients have mutations in a protein complex called the cohesion complex, which plays an essential role in regulating cell division. Zuzana plans to investigate how cohesin mutations affect a process called DNA looping. Her hypothesis is that malfunctions in DNA looping lead to the development of MDS and other blood diseases.
Anne Carpenter is a pioneer in building scalable, user-friendly technologies for extracting data from images. She directs a lab of biologists and computer scientists who develop and use advanced machine learning methods to identify important patterns in cell populations. Anne’s team is best known for developing CellProfiler, the first open-source software for cell–image analysis.
New therapies are urgently needed for patients with psychiatric disorders, but developing these drugs is an especially lengthy process. Anne’s lab wants to accelerate the timeline by finding new, efficient methods to test potential therapies in the early stages of their development.
Aleks Goeva is a statistician specializing in machine-learning models for understanding the human brain.
The human brain is one of the most complex structures in the living world. For centuries, scientists have struggled to understand it. Only in the past few years have state of the art tools like single-cell technologies and 3D cellular models offered hope of gaining insight into the workings of the brain—not to mention mystifying disorders such as schizophrenia, autism, and Alzheimer’s. But they’re also generating unprecedented amounts of data that labs are currently ill-equipped to handle. For her project, Aleks is experimenting with a novel data-analysis method to tackle this growing mountain of data.
Rajat Gupta is a cardiologist and vascular biology researcher who uses stem cell–derived and genome-edited vascular cells to understand coronary artery disease.
Every year, hundreds of thousands of people in the U.S. die of sudden cardiac death. And, as vital as this area of study is, we still don’t know a lot about a crucial factor: heart cells. Working with clinical partners, Rajat will investigate heart cells in coronary blockages for data that can abet our ability to predict who is most at risk for sudden cardiac death.
Yonatan Grad is a physician-scientist studying infectious diseases and how pathogens evolve and spread throughout populations.
Yonatan will collect and study strains of Neisseria gonorrhoeae, the bacteria that causes gonorrhea, from the Himba, a nomadic, pastoralist tribe of 50,000 people in northern Namibia. The Himba have very high rates of infection—more than 60 percent of adults carry the bacteria—but very low rates of symptomatic disease. Yonatan is using his BroadIgnite award to support travel to Namibia, collect specimens, and conduct DNA sequencing. This work will lead to important insights that will impact the understanding and treatment of antibiotic-resistant gonorrhea—a rising global public health threat—as well as other infectious diseases.
Jamie Marshall leads a collaboration aimed at unraveling the molecular mechanisms of kidney disease to develop targeted therapies.
Chronic kidney diseases afflict 500 million people worldwide, yet many patients face limited treatment options. Understanding the genes, proteins, and pathways involved in the organ’s deterioration can give patients early—and potentially lifesaving—diagnoses and therapies. Jamie will use her BroadIgnite funding to create cellular maps of the kidney that give researchers a fuller picture of different cell types and interactions—and what happens when they malfunction.
Karin Pelka studies cancer immunology—which focuses on how to harness a patient’s own immune system to attack tumors.
Colorectal cancer is the second-leading cause of cancer death in the U.S. While recent developments in checkpoint inhibitors—an important class of cancer immunotherapies—hold great promise, most patients do not respond to these powerful drugs, for reasons that remain unclear. Karin wants to find out why by using her BroadIgnite funding to analyze colorectal tumors from patients at MGH.