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 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, aggregated hundreds of thousands of SARS-CoV-2 sequences from researchers around the world to trace the virus’ distinct mutations as it spread across different geographic regions. Researchers freely used 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. Funds from Alina's 2020 BroadIgnite award enabled her to expand the capabilities of the site and incorporate data from hundreds of thousands of new SARS-CoV-2 genomes to capture developing trends during 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.

Large biological datasets have enormous potential in helping to answer important questions on human health and disease but they are challenging to study, especially when dissecting individual data inputs—an issue known to perpetuate biases against marginalized groups. Sam, who previously worked on visualizing data at Apple, will address this as a BroadIgnite awardee by developing machine learning methods to identify and mitigate biases in large biological datasets, including those involving sex and race.

Sumaiya has uveitis, a rare autoimmune disease causing inflammation of her retina and impairing her vision. As a rare disease patient, she wants to help others like her by investigating the mechanisms underlying monogenic diseases, single-gene disorders that make up most rare genetic diseases. As a BroadIgnite awardee, she will study how single amino acid mutations dictate the structure and functions of proteins—thus, setting the stage for more effective precision medicine treatments for rare monogenic genetic disorders.

Augustin co-developed CellBox, a machine learning–based algorithm that models cell dynamics to predict responses to a range of perturbations—a capability that could aid the discovery of combination cancer drug therapies. However, these models do not fully capture protein-level information, and most cancer drugs target certain proteins. As a BroadIgnite awardee, he aims to generate large-scale single-cell proteomics data and leverage machine learning algorithms (like CellBox) to better understand the biological mechanisms driving cancer, and identify new treatments that can mitigate drug resistance.

About 90 percent of the DNA in the human genome does not encode proteins. Scientists have only just begun to get a glimpse of the critical role that the non-coding genome plays in health and disease. Fadi plans to use his BroadIgnite funding to delve into non-coding elements—including enhancers, which activate the expression of certain genes—in order to find novel therapeutic targets for cancer.

Immune mechanisms are constantly changing to maintain the body’s homeostasis, making it challenging to decipher these processes and make precise diagnoses of disease in clinic. Yakir, a rheumatologist and trained computer scientist, will use his BroadIgnite funding to analyze blood samples using advanced machine-learning approaches, detailing a quantitative picture of how immune states vary in both health and disease. With this map, doctors can someday precisely identify—and treat—the root cause of a patient’s immunological dysfunction.

Autoimmune diseases like systemic lupus erythematosus (SLE) disproportionately affect women, especially those that identify as Black or Latinx, more than men. However, all patients diagnosed with SLE are treated with the same immunotherapies. BroadIgnite funding will allow Ayshwarya to deploy single-cell sequencing and computational methods and dissect such phenotypic heterogeneity, paving the way for personalized treatments that better manage patients’ symptoms.

While scientists understand how organ-level dysfunctions can affect the body, it remains harder to uncover and therapeutically manipulate their core driving mechanisms—Constantine describes it as seeing a crashed car with a broken windshield but not knowing what caused the crash itself, like worn-out brake pads. His BroadIgnite project seeks to couple experimental platforms, such as photochemistry-based spatially-resolved-omics technologies, with computational approaches to investigate the drivers of cells' beneficial or pathologic responses to disease, with applications across cancer, autoimmunity, and infection.

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Somatic mutations occur over the course of the lifetime, and as a gastroenterologist, Yousef investigates how these changes influence benign gastrointestinal diseases. With his BroadIgnite funding, he plans to leverage clinical samples from Massachusetts General Hospital (MGH) and the MGB Biobank to investigate somatic mutations in three different inflammatory gastrointestinal diseases—microscopic colitis, eosinophilic esophagitis, and a colitis caused by cancer immunotherapies—to decipher how they impact these conditions.

Changes in the cellular organization of tissues impact a range of diseases, including autoimmune disorders, neurodegenerative conditions, and cancers. Indeed, tumor progression hinges upon the cellular composition of surrounding tissues. As a BroadIgnite awardee, Salil will apply AI to molecular and genetic datasets to identify regions of the genome that control how cells are arranged in tissues—work that can someday inform effective new therapies for patients.

To tackle rare kidney disease, Matt will draw upon his training in physiology and biomedical engineering and apply multiplexed imaging—which can capture thousands of cellular features simultaneously—to detail the molecular processes that disrupt cellular homeostasis in kidneys. His BroadIgnite work will not only improve our understanding of kidney disorders but also accelerate biomarker discovery, enabling researchers to better understand and measure disease progression.

All cells have the same genetic code—what determines their type, state, and function is gene expression. However, much of what regulates gene expression is still poorly understood. Elisa's BroadIgnite project seeks to leverage common genetic variants to study regulatory regions of the genome, which control gene expression and are critical to understanding human disease. Specifically, she will use differentiated stem cells to glean insights into how genetic variants drive regulatory changes in liver cells and apply this knowledge to understand metabolic diseases.

How specific antibodies and antigens bind to one another informs a range of treatment strategies, including cancer immunotherapies. However, current methods only allow researchers to evaluate only one or just a few interactions at a time. Wengong seeks to change this with his BroadIgnite award, and plans to build a novel deep-learning model to predict multiple antibody–antigen binding relationships at once—a tool that can advance disease areas, such as cancer, autoimmune disorders, and infectious disease.

Genome-wide association studies have linked genetic variants to specific phenotypes and disease risks, but we still do not fully grasp how these variants impact biological processes, or have the tools to identify variants that may emerge in the future. With his BroadIgnite project, Konrad plans to address this gap by analyzing the genetics of healthy individuals to detail the landscape of genetic variants—both common and rare—and link them to biological functions. Importantly, he will also build tools to predict new variants, including those that do not exist within the population yet as well as ones that have not been identified in studies so far.

The human immune system changes over a lifetime, which can pose challenges to one’s health. For instance, elderly people often have a harder time responding to vaccines compared to the younger population. As a BroadIgnite awardee, Sophia seeks to create spatial transcriptomics tools to capture T cells and B cells in adaptive immunity that drive these changes—in response to disease, aging, or pregnancy—and inform approaches that can rejuvenate immunity in these contexts.

Directed evolution—which mimics the natural evolutionary process in a laboratory setting—holds the potential to accelerate the pace of scientific research, but has yet to be optimized across a range of systems. With her BroadIgnite award, Amanuella aims to tackle this challenge, and optimize directed evolution techniques in systems, ranging from bacteria and yeast to plant and mammalian cells.

As an oncologist at Dana-Farber Cancer Institute, Erin has seen how quickly a patient’s indolent lymphoma can transform into a drug-resistant or rapidly growing cancer, making it extremely difficult to treat—a transformation poorly understood by scientists. Erin’s BroadIgnite project seeks to change this by using single-cell technologies to pinpoint the cellular changes that occur during this dramatic progression, ultimately identifying targeted treatment opportunities for aggressive lymphomas.

Physicians currently rely on medical imaging to detect tumors in patients and monitor those in remission, but this method has limitations and a patient’s cancer can go unnoticed until it has already metastasized. To tackle this, Shervin, who is a radiation oncologist at Massachusetts General Hospital, will leverage his BroadIgnite funding to build tools that can detect microscopic levels of tumor DNA in patient blood samples for early, non-invasive cancer diagnosis.

Genetic therapies hold tremendous potential to treat diseases and improve human health, but their success relies on accurate systems that can deliver these treatments precisely to specific organs and cell types. As a BroadIgnite awardee, Josh aims to help bring promising genetic medicines closer to the clinic by elucidating the mechanisms by which secreted proteins reach their target destinations in the body—processes that can someday be harnessed to deliver treatments precisely to specific cell types.

Blood cancers arise from mutations in bone marrow stem cells, and nearly 50 percent of these mutations are due to defects in splicing—an essential regulatory process where noncoding regions of the genome and coding regions are joined together to generate various proteins. With BroadIgnite support, Mounica, who is an oncologist at the Dana-Farber Cancer Institute, will deploy a novel approach to systematically map how dysfunctions in splicing impact the progression of blood cancers, eventually informing new much-needed treatment strategies.

Despite major advances in genome sequencing technologies over the past few decades, the majority of individuals with a suspected genetic disease still lack a confirmed diagnosis. This unmet need is especially prevalent for neurogenetic disorders. As a neurologist at Brigham and Women’s Hospital, Vijay will tackle this challenge with his BroadIgnite project. Specifically, he will partner with the Broad Proteomics Platform, deploying machine-learning approaches to develop an assay that detects protein expression outliers from individuals with unsolved rare genetic diseases. Vijay’s goal is to develop a scalable method from clinically-accessible tissues that can both augment novel gene discovery and resolve variant-to-function associations, ultimately shortening the diagnostic odyssey for patients and potentially informing tailored genetic therapies.

Fungal pathogens, such as Candida albicans, cause some of the most prevalent and deadliest infections in patient populations. Yet there are only a few effective antifungal therapeutics. Hannah is working to change this. With her BroadIgnite award, she will profile fungal extracellular vesicles—membrane-bound particles secreted by fungi that help infect the host—and investigate how the host immune system responds to them. This work can yield crucial insights into the biology of fungal pathogens, pointing researchers toward new antifungal strategies.

The human microbiome—the community of microorganisms (such as bacteria, fungi, and viruses) that live in and on the human body—impacts a variety of biological processes in both health and disease. But the molecular mechanisms driving this microbiome–host crosstalk remain poorly understood. For her BroadIgnite project, Soumya plans to develop high-throughput strategies to identify interactions between the microbiome proteins found throughout the human body, including the gut, mouth, skin, and more, and human proteins as well as characterize their biological functions—research that can eventually decode microbiome-associated disease pathways.

As a dermatologist at Harvard Medical School, Jennifer has seen how immunotherapies, such as immune checkpoint inhibitors, can treat melanoma—a type of aggressive skin cancer—effectively in some patients but not others. Her BroadIgnite project seeks to understand this variability in patient response using recently developed spatial sequencing approaches in mouse models and patient samples. She aims to uncover mechanisms underlying resistance to checkpoint inhibitors in melanoma; identify ways to promote patient response to treatments; and test novel immunotherapy strategies.

Throughout our lives, the nonreproductive or somatic cells in our bodies are constantly undergoing DNA mutations—changes that can sometimes lead to an increased risk of cancer and other diseases. Andrew’s BroadIgnite project seeks to better understand the genetic landscape of somatic mutations; how they are acquired by cells and tissues as we age; and how they contribute to human disease. For this, he will build novel sequencing tools and enhance a technology he has already pioneered, called Slide-tags, that allows researchers to deeply profile individual cells while also retaining their spatial locations as well as information on their cellular environment. (This information is often lost in traditional sequencing techniques.)

All cells in the brain are covered in carbohydrates, such as heparan sulfate (HS), which plays a critical role in forming neuronal connections as well as in neurodegenerative conditions like Alzheimer’s disease. However, it has long been challenging to study this important carbohydrate without removing it from its biological context. As a BroadIgnite awardee, Shiwei will tackle this by building a set of novel optical sequencing tools that can visualize and profile individual HS molecules in intact biological samples—work that can advance our understanding of HS and its neurobiological functions.

This year, the first-ever CRISPR-based gene therapy was approved for use in sickle cell disease patients. While this is a powerful example of how gene therapies are transforming treatments, the field still faces a major challenge: creating safe delivery vehicles that can send gene therapies to the right cells in the right organs. One promising option is deactivated viruses. Shai will use her BroadIgnite funding to leverage machine-learning approaches and create a pipeline for engineering new and robust viral delivery vehicles that can be easily targeted to specific cell types—improving gene therapy efficacy and reducing side effects.