Faculty Scholars Program

Infectious bacteria use toxins called effector proteins to invade host cells. Neal Alto studies how these proteins operate, with an eye toward uncovering new therapies to combat diseases caused by Escherichia coli, Shigella, Salmonella, and other microorganisms. He's also looking to harness effector proteins to explore the causes of auto-inflammatory diseases and cancer.

Alexei Aravin's previous research led to the discovery of a group of small, non-coding RNAs called piRNAs. Now, he is studying the molecular mechanisms behind the piRNA pathway and investigating how these RNAs protect germ cells against mutations caused by transposons – segments of genetic material that undergo relocation within the genome.

Michel Bagnat investigates how fluid secretion and hydrostatic pressure can shape the form and function of organs. Focusing his work on the spine and the intestine, he has found that faulty fluid regulation during early development can lead to conditions such as scoliosis and secretory diarrhea.

Siobhan Brady maps the gene networks that regulate the development of plant roots. Comparing these networks in different cell types across different species, including important crops such as tomato and sorghum, reveals how some plants adapt to frequent droughts and other harsh environmental conditions.

Ken Cadwell studies how humans have adapted to the infectious agents that inhabit the gastrointestinal tract, looking for potential triggers of inflammatory bowel disease. His research has also revealed that, in the right contexts, normally harmful viruses and parasitic worms can provide some surprising benefits to their hosts.

Fernando Camargo's work with adult stem cells has helped describe the Hippo pathway, a stem cell regulatory system that controls the growth of organs and tumors. He also developed a new strategy that uses transposons to track stem cell lineages in situ, allowing him to investigate how blood cells are produced in bone marrow.

By figuring out how the human auditory cortex responds to spoken sounds, Edward Chang is studying how the brain interprets verbal communication. His research reveals a major role for the brain’s superior temporal gyrus region in speech perception, and may shed light on the neural circuitry involved in language learning.

A fundamental problem in neuroscience involves understanding how synapses are assembled in living animals to produce behaviors and store memories. Daniel Colón-Ramos uses the nematode Caenorhabditis elegans to explore this question, examining the biological mechanisms cells use to create synapses during development, maintain them during growth, and modify them during learning.

José Dinneny looks at the mechanisms plants use to sense water availability and adapt to drought conditions. He takes a holistic approach in his research, emphasizing the importance of developmental pathways and molecular genetic mechanisms in guiding acclimation and homeostatic processes.

Victoria D'Souza is using nuclear magnetic resonance to understand how retroviruses employ various RNA structures to aid in the transcription and translation of their genomes. By mapping the three-dimensional topology of viral nucleic acids, she hopes to learn more about how these molecules interact with host molecular components and how new therapeutics could potentially interfere with these interactions.

Maitreya Dunham uses comparative genomics and experimental evolution techniques to investigate how yeast genomes evolve over time periods ranging from a few weeks to millions of years. Her research may lead to therapies that counter the evolution of drug resistance in fungal and bacterial pathogens, viruses, and cancer.

Alex Dunn's laboratory uses sophisticated biophysical measurements to better understand how cells work together to build complex, multicellular tissues. His team seeks to learn how to guide cellular assembly in the context of tissue engineering, and to understand what goes wrong in diseases such as cancer, in which cells fail to work together to achieve their proper physiological function.

Ila Fiete builds theoretical models and numerical simulations while working closely with experimentalists to design experiments and analyze neural data, with the goal of understanding how the brain solves hard problems such as spatial navigation using components that are forgetful and noisy. Her focus is on circuits that underlie short-term memory, integration, and inference in the brain.

The bacteria that reside in and on the human body produce a wealth of small molecules, many of which play crucial roles in human physiology and disease. Michael Fischbach is examining the functions of these molecules, some of which may eventually be used to treat immune, metabolic, and neurological disorders.

One of the central challenges in neuroscience is distinguishing how modification of synapses and neural circuits can change behavior. Robert Froemke is investigating this question by studying the circuits and molecular cues used by rodents when they give birth to and care for their offspring.

Adam Frost studies the molecular machines that are too fragile to purify, too large or flexible to crystallize, or are dependent on lipids that cannot be replaced by detergent micelles. To do this, he integrates cryo-EM with genetics, biochemistry, and diverse imaging techniques.

Antonio Giraldez is interested in how fertilized eggs develop into complex multicellular embryos. Using zebrafish as a model system, he is looking at the mechanisms that activate the genome after fertilization and how this universal transition drives post-transcriptional regulation of the maternal instructions.

Amy Gladfelter is looking at how the physical properties of molecules lead to cell organization and function. Her research focuses on two areas: how multinucleate cells are organized in time and space, and how cells perceive their shape and use geometry to inform signaling and decision making.

Andrew Goodman's research is focused on dissecting the mechanisms that human commensal microbes use to cooperate, compete, and antagonize each other in the gut. His team works to understand how the communities that develop from these interactions influence our responses to pathogens and medical drugs.

Valentina Greco is investigating how stem cells initiate and coordinate tissue regeneration, both to maintain healthy tissues and to restore damaged tissue after injury. She is also investigating how regenerating tissues respond to the presence of cells with cancer-promoting mutations, seeking a better understanding of the earliest events in tumor development.

Elissa Hallem is investigating how parasitic worms use sensory cues such as heat and odors to find their hosts. Her studies of neural circuits in skin-penetrating roundworms, as well as in the free-living roundworm Caenorhabditis elegans, focus on how the worms detect sensory cues and how the brain responds differently to those cues under different circumstances.

Elizabeth Haswell is studying how plants use mechanosensitive ion channels to sense and respond to mechanical forces such as tension, touch, or vibration. She is also developing research tools that will enable her to measure membrane tension in live cells and to explore electrical signaling during trap closure in a carnivorous aquatic plant.

Mitochondria, cells' tiny power plants, are essential for many cellular activities, and their dysfunction is associated with aging, metabolic disorders, Parkinson's disease, bacterial infections, and cancer. Cole Haynes is investigating the mechanisms cells use to monitor their mitochondria and, when faulty, the strategies employed to ensure cell survival and mitochondrial recovery.

Lin He is identifying functionally important, non-protein coding elements of the mammalian genome and then characterizing what they do, how they work, and how they are regulated. Her studies focus on a class of gene-regulating non-coding RNAs called microRNAs and a class of mobile elements called retrotransposons, both of which have wide-ranging impacts on development and disease.

Ekaterina Heldwein is using structural biology to learn how herpes viruses get in and out of host cells. Her lab is working to develop a comprehensive, atomic-level map of the ways herpes viruses manipulate their hosts, with the ultimate goal of devising antiviral drugs that interfere with those interactions.

To enable detailed studies of how molecules enter and exit cell nuclei – and how disruption of that process contributes to disease – André Hoelz is focusing on the nucleus's only gateway: the nuclear pore complex. He is developing an atomic-level model of the mega assembly, which is made up of about a thousand proteins, and working toward reconstituting it in the test tube.

Katrin Karbstein studies how ribosomes – large cellular complexes that manufacture proteins – assemble and how cells ensure that new ribosomes are fully functional. She is also investigating what happens when ribosome quality control mechanisms are bypassed and how faulty ribosomes compromise human health.

Ming Li is unraveling the signaling pathways that regulate immune system homeostasis, tolerance, and immunity. He is particularly interested in understanding how immune responses to tumors are distinct from those to healthy or infected tissue. Ultimately, he wants to use this knowledge to develop new cancer therapies.

In mammals, odor-detecting neurons each produce a single type of olfactory receptor, which is chosen from a pool of thousands. Stavros Lomvardas is studying the mechanisms that determine which olfactory receptor gene is switched on in an individual cell, with the larger goal of understanding how cells orchestrate random choices that generate diversity.

David Masopust is investigating how immune cells find and respond to infection in the mucosal membranes that line the respiratory, intestinal, and reproductive tracts. Better understanding of these processes could change the way researchers think about vaccine design and cancer immunotherapies.

Coleen Murphy studies the molecular processes that regulate longevity, reproductive aging, and cognitive decline using the model system Caenorhabditis elegans. By identifying the active genes in each of the worms' tissues, she aims to enable new understanding of how biological processes change with age and how they can be manipulated to slow the declines that impact quality of life in humans.

Mala Murthy is studying how the brain modulates behavior in response to dynamic sensory cues, using the acoustic communication system of fruit flies as a model. Flies use acoustic signals during courtship, and she is characterizing the neural activity underlying both the patterning of courtship song structure in males and the processing of song in females.

Markus Müschen explores oncogenic signaling in B cell-derived leukemia and lymphomas. Unlike other types of cancer, B cell tumors are subject to an autoimmunity checkpoint. As with normal B cells, B cell tumor cells are weeded out if they are self-reactive. Müschen uses pharmacological agents to engage autoimmunity checkpoints in B cell tumors, with the ultimate goal of overcoming resistance to conventional drug-treatment.

Celeste Nelson investigates the physical factors that govern embryonic tissue development and cancer using mouse and human lung and mammary gland as model systems. A clear understanding of the biochemical and physical cues directing embryogenesis may help identify the origin of certain congenital conditions and clarify how development can go awry.

Jennifer Nemhauser studies plant signaling pathways to learn how multicellular organisms develop and respond to their environment. She gleans information about molecular networks in natural systems and then synthetically programs these core functions into yeast cells to measure the effect of evolved and engineered changes. Her ultimate aim is to develop technologies that support small-hold farmers and foster global health.

Malaria continues to impact global human health, and Jacquin Niles wants to change that. Niles studies functional genetics in the malarial pathogen Plasmodium falciparum, as well as pathogen-host interactions. He's working toward a clearer understanding of the parasite and disease to provide the scientific foundation for new malarial diagnostics, treatments, and prevention/elimination strategies.

For the intestine to carry out digestive functions and act as a chemical and bacterial barrier, its cells must be replenished at a high rate. This steady cellular turnover requires highly controlled mechanisms of regeneration. Benjamin Ohlstein investigates the regulatory pathways that control intestinal stem cell behaviors necessary to maintain balance in the tissue.

Clodagh O'Shea wants to understand the mechanisms of cancer growth, and she has turned to a common respiratory pathogen, adenovirus, for help. O'Shea discovered that adenovirus genetics and replication machinery hint at how cancer proliferates. Using the virus as a model, she hopes to decipher the principles that govern cancer growth and apply that knowledge to create more effective treatments.

Julie Pfeiffer discovered that gut bacteria can inadvertently advance enteric viral infections by influencing viral replication and transmission. Now, using poliovirus and reovirus as models, Pfeiffer is exploring this connection further to better understand how viruses in general may depend on intestinal bacteria for their survival.

As immature cells grow and differentiate, gene-expression patterns shift accordingly to lock in a single cell fate. Kathrin Plath wants to determine how adult cells can be specifically and efficiently reprogrammed to return the cell to a pluripotent, undifferentiated state. More broadly, Plath is interested in the molecular mechanisms that control genome organization, chromatin, and gene expression.

Manu Prakash is a biophysicist who studies simple animals to better understand how a small collection of cells gives rise to a multicellular organism. He develops new imaging tools and techniques based on soft matter physics that aid in his quest to understand the origins of complex behavior in simple animals. Along the way, he is also developing novel tools for "frugal science" applied to global health and democratizing access to scientific experience.

Shu-Bing Qian researches mRNA translation and the mechanisms that regulate the onset of protein synthesis under certain cellular conditions. A clearer conception of the factors that control the quality and quantity of protein production during events such as cell growth, differentiation, or stress response could help define new therapeutic strategies for diseases such as cancer, diabetes, and neurodegenerative diseases.

Tissue regeneration requires significant coordination among numerous cell types. Understanding this finely choreographed process drives Jayaraj Rajagopal's research. Rajagopal employs an outside-the-body model of lung regeneration to analyze the principles that govern cellular ensembles in organs and human disease.

John Rinn was one of the first to discover that the human genome hosts thousands of new long noncoding RNA genes. He has dedicated his research to understanding how these genes contribute to human health and disease. He further aims to dissect the molecular grammar guiding their functional roles in hopes of finding new avenues of therapeutic intervention.

Inflammation plays a critical role in the immune response. Left unchecked, however, it can cause chronic inflammation, trigger autoimmune disorders, or fuel cancer. Carla Rothlin studies the biochemical mechanisms that control immune response activation and intensity, with an eye toward inflammation. A better understanding of immune system regulation could lead to new treatments for inflammation-associated diseases.

Michael Rust combines mathematical modeling and wet lab experiments to investigate how the circadian clock, a molecular oscillator, controls daily fluctuations in metabolism and energy use in cyanobacteria. These daily rhythms are likely to provide growth and survival advantages to cells.

Frank Schroeder investigates how previously unidentified products of cell metabolism function as signals between individuals and within cells in the worm Caenorhabditis elegans, an important model system for human disease. These small molecules exhibit fascinating chemical diversity and regulate lifespan, reproduction, behavior, and many other phenotypes, often via signaling pathways that are evolutionarily conserved throughout the animal kingdom.

Song-Hai Shi uses imaging, mouse genetics, and electrophysiology to dissect the molecular and cellular mechanisms that control the formation and operation of neuronal circuits in the mammalian brain. These circuits account for critical brain functions such as sensory perception, movement, and reasoning.

Jan Skotheim studies how yeast and animal cells control their size by coordinating growth and division. As cells grow, some regulatory molecules inhibiting cell division are diluted, while other regulatory molecules activating cell division are not. This produces a size-dependent biochemical signal through which cell growth triggers division.

Agata Smogorzewska studies how DNA is maintained during DNA replication. She is guided by human genetic diseases that are caused by mutations in DNA repair genes and strives to understand the mechanism by which lack of the proper DNA repair predisposes patients to cancers and bone marrow, kidney, and liver failure.

Daniel Stetson studies how our cells detect infection with a virus. Sensors of foreign DNA and RNA are essential for activating immune responses to viruses, but they can also cause severe autoimmune disease if they are not properly regulated. Stetson's lab seeks to understand this dichotomy of protective immunity and autoimmunity activated by the same antiviral sensors.

Francesca Storici is studying how cells use RNA as a template to repair DNA lesions in a process in which genetic information flows in reverse from RNA to DNA. Furthermore, during DNA metabolism, subunits of RNA can be incorporated into the genome, and Storici is investigating spectra, consequences, and whether these RNA intrusions are associated with cellular stress and/or cancer.

Gurol Suel studies how bacteria coordinate their behavior to collectively organize into communities called biofilms, which have a higher resilience against antibiotics. His research suggests that, similar to neurons in the brain, bacteria use electrical cell-to-cell signaling mediated by ion channels to coordinate their action.

Sohail Tavazoie investigates the roles of small noncoding RNAs and proteins that alter the biology of distant organs and facilitate their colonization by metastatic cancer cells. His work has led to the development of anti-metastatic small molecules that are advancing to clinical trials. These studies have also provided basic insights into mechanisms of gene regulation.

Matthew Vander Heiden uses mouse models to understand how cancer cells alter their metabolism to meet the requirements of growth and proliferation. Identifying rate-limiting steps in critical metabolic pathways, such as the breakdown of glucose and the production of the basic subunits of DNA, may lead to new cancer therapies.

Jue Wang is studying the conflicts between the replication and transcription machineries in bacteria, which are exacerbated by stresses such as nutrient deprivation or exposure to antibiotics. She is characterizing how such conflicts have shaped the evolution of microbial genomes, and how conflicts are avoided by coordinating cellular metabolism in response to stress.

Sing Sing Way studies how genetically foreign maternal and fetal tissues coexist during pregnancy and how babies respond to commensal and pathogenic microbes during the early newborn period. Understanding how the immune system works in each of these unique developmental contexts may lead to new therapeutic strategies for improving pregnancy outcomes and protecting newborn babies against infection.

Marius Wernig investigates the molecular mechanisms that determine cell lineage identity, focusing on reprogramming skin and stem cells into functional neurons. His work includes translational efforts to treat an incurable genetic skin disease and various diseases of the nervous system such as multiple sclerosis.