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.

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.

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.

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.

Eli is using BroadIgnite funding to study exceptional responders—cancer patients who respond extremely well to new immunotherapies.

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.

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.

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.

Listen to the BroadIgnite Podcast with Sara Jones

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.

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.

Listen to the BroadIgnite podcast with Moran Yassour

Read about Moran's research in The Atlantic

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.

Read about Nikhil's research in the Wall Street Journal

Watch a video about the Metastatic Breast Cancer Project

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.

Read about Sidd's research in the New York Times

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.

With BroadIgnite funding, Alex plans to build a new open-source computational tool to expedite diagnosis of a wide variety of diseases.

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.

Watch a video about Viktor's research

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.

Listen to the BroadIgnite Podcast with Elinor Karlsson

Read about Elinor's research in the New York Times

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.

Listen to the BroadIgnite Podcast with Dan Neafsey

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.

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.

Read about Amit's research in MIT Technology Review

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.

Listen to the BroadIgnite Podcast with Evan Macosko

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.

Watch Mariella pitch her BroadIgnite project

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.

Watch Oliver pitch his BroadIgnite project

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.

Watch Sam pitch her BroadIgnite project

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.

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.

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.

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.

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.

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.

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.

Katie will use her BroadIgnite award to investigate how immune cells thwart invaders like carcinogens and allergens. Using a new technology that provides rapid readouts of cellular response to multiple stimuli, she will douse batches of immune cells with asbestos and other triggers—and evaluate the results. If successful, the experiment will shed light on potential treatments and provide a more efficient way to test them.

Personalized cancer vaccines—which train a patient’s immune system to identify and destroy tumors while sparing healthy tissue—may be a game changer in immunotherapy. Susan will use her BroadIgnite award to hone a new technology that can improve the specificity with which researchers customize these vaccines.

Metabolic syndrome—a cluster of risk factors that increases one’s susceptibility to heart disease, diabetes, neurodegenerative diseases, and obesity—has reached epidemic levels across the globe. But there’s still a lot we don’t know a lot about the molecular mechanisms behind this disorder—making it difficult to develop therapies. Nicolas hopes to lay the groundwork for new therapies by investigating one of the most poorly understood causes of metabolic diseases: how excessive exposure to certain fats can damage cells and tissue.

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.

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.

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.

New molecular imaging technologies have made many exciting discoveries possible in recent years—from the structures of proteins and drug targets involved in cancer to how SARS-CoV-2 binds to human cells. However, current techniques often don’t scale well, and therefore, can’t measure the large number of molecules required to investigate the toughest questions about diseases such as schizophrenia or diabetes. With BroadIgnite support, Mehrtash will explore ways to resolve this limitation using machine learning and new molecular barcoding techniques. Ultimately, he aims to develop a method that can simultaneously profile the complete microscopic state of thousands of cells, at single-molecule resolution, much more quickly and efficiently than current methods.

To contribute to global research efforts against the pandemic, Alina recently led the launch of a new open-source website to track the genetic evolution of SARS-CoV-2. The site, called COVID-19 Coronavirus Genetics, has aggregated hundreds of thousands of SARS-CoV-2 sequences from researchers around the world to trace the virus’ distinct mutations as it spreads across different geographic regions over time. Researchers can now freely use this online resource to answer critical questions about the coronavirus, including which genetic variants to test new therapeutics and diagnostics on before implementation in a specific region. BroadIgnite funds will enable Alina and her collaborators to dramatically expand the capabilities of the site and incorporate data from hundreds of thousands of new SARS-CoV-2 genomes over the next years to capture developing trends in the pandemic.

Malaria infects more than 230 million people every year, and drug-resistant strains are rising. To stop this deadly endemic, researchers need new diagnostics—current tests are not sensitive enough to detect new strains or require expensive laboratory set-ups. Kiran has a solution. He’s developing a method that amplifies the genetic material of malaria so that it can be sequenced using 1/500th of the usual amount of required DNA. Unlike conventional techniques, Kiran’s method requires no special equipment, making it especially useful in remote, resource-limited areas. Kiran will use his BroadIgnite funds to hone this new technology and test its effectiveness on various strains of malaria. His hope is to develop a new frontline diagnostic test to aid malaria surveillance efforts in Africa.

How are bats able to harbor coronaviruses—like SARS, MERS, and SARS-CoV-2—without getting sick? Diane plans to shed light on this biological mystery by using her BroadIgnite award to compare gene expression patterns in human, ferret, and bat cells experimentally infected with SARS-CoV-2. Drawing on the genomic similarities and shared evolutionary history of mammals, Diane aims to identify genetic features that allow bats to tolerate this deadly pathogen, potentially pointing to new therapeutic insights for Covid-19.

Interactions between proteins—the tiny molecules that keep us alive—play a vital role in driving tumor growth, making them important targets for new drugs. However, they’ve been difficult to hit. Alessandra, a physician-scientist in the Sellers Lab, hopes to help solve this challenge by developing a technology that illuminates protein–protein interactions on a single-cell basis. This would allow researchers to identify how proteins engage and communicate with each other much faster and cheaper than current methods, thereby accelerating the pace of new drug discovery.

Jacob led a major research effort that sequenced 772 SARS-CoV-2 genomes to trace how the virus spread across the Boston area during the first wave of the Covid-19 pandemic. This type of genomic surveillance works by cataloging the distinct mutations that a virus accumulates as it is transmitted from person to person. With BroadIgnite support, Jacob will expand upon this work and test whether monitoring these mutations in real time can help contact tracing efforts in Massachusetts. By collecting and analyzing genome sequences of SARS-CoV-2 from Boston-area hospitals every week for the next six months, his hope is to detect—and alert public health experts to—new clusters of Covid-19 in the area before they spread.

Stem cells are vital to human health. But we still don’t know the answers to some of the most basic questions about them—such as how many populate our bodies and how they change with age. Leif, a physician-scientist in the Regev Lab, intends to answer these questions by tracking lineages of mutations in human stem cells, similar to building a family tree, using genome sequencing. His work could open new doors for understanding how stem cells contribute to cancer and other blood-related diseases.

Aziz recently pioneered a new technology, called MAS-seq, that timestamps RNA sequencing data, allowing researchers to better investigate individual cells’ behaviors at a specific moment in time, making it possible to capture complex cellular dynamics, such as how tumor cells evolve. Aziz will use his BroadIgnite funding to take MAS-seq to the next level, ensuring its accuracy and rigorousness for studying disease.

Scientists have uncovered several genetic risk factors for Alzheimer’s disease; however, your DNA alone seldomly determines whether you are at risk of the disease. Juli wants to uncover the role that other health factors, such as metabolic disorders like obesity and diabetes, play in Alzheimer’s development by investigating how neurons handle the metabolic stress induced by Type 2 diabetes. Her goal is to unravel how specific genetic risk variants are influenced by diabetes-related changes and how they can be interrupted to halt disease progression.

European ancestry populations, which compose just 16 percent of the global population, make up about 80 percent of participants in genetic studies. Thus, research short-changes almost all other populations and misses vital insights into the genetics associated with human health and disease. Alicia wants to help remedy this bias by using her BroadIgnite grant to sequence more than 3,000 genomes from 14 countries spanning sub-Saharan Africa and to ensure the data is widely accessible.

Ralda wants to unravel the biology underlying a rare, incurable genetic disease called 22q11.2DS in order to eventually help find potential treatments. Caused by a tiny deletion of chromosome 22, 22q11.2DS affects an estimated 1 in 4,000 people and results in devastating consequences, including heart defects, severe developmental delays, and facial malformations. Using stem cells that her lab has collected from 50 patients, Ralda will investigate the underlying biological mechanisms of 22q11.2DS-associated heart defects in hopes of elucidating new avenues for therapeutic discovery.

Severe Covid-19 and sepsis share similar symptoms—multi-organ failure, shortness of breath, fever, confusion—and both are associated with dysregulated immune response. Miguel and his team recently discovered another connection: The blood cells of patients with severe forms of these diseases have different baseline gene expression profiles than those with mild infection. With BroadIgnite support, Miguel wants to expand this work to identify which immune response pathways are altered in these patients—and whether they can be harnessed as new treatment avenues.

While antibodies have gained attention in the Covid-19 pandemic, it’s increasingly clear that T cells—which target and destroy pathogen-infected cells—also play an important role in helping patients fight infections—and develop immunity. During the past year, Shira led a significant discovery in how T cells help defend against SARS-CoV-2: She identified foreign protein fragments, called peptides, that sit on the surface of SARS-CoV-2–infected cells and signal for help from T cells. BroadIgnite funding will allow Shira to delve deeper into the exact mechanisms that control this response—a crucial line of inquiry that could inform the development of vaccines that better recognize the virus.