Speaking of Science (The Intramural Research Program of the National Institutes of Health (NIH))

Finding treatments for mental health conditions doesn't just deal with people who live with them. Healthy volunteers play a critical part in the science of understanding our brains and behavior. But what qualifies as "healthy" can vary across labs and skew how scientists interpret study results. Dr. Joyce Chung, the Deputy Clinical Director at the National Institute of Mental Health (NIMH), is changing that. She is creating a pool of vetted volunteers to bolster the integrity, efficiency, and safety of mental health research.

Dr. Peter Bandettini spends a lot of time peering into people's heads. Not because he is clairvoyant, but because he is a biophysicist. Using functional MRI (fMRI), a revolutionary neuroimaging technique he helped pioneer in the '90s, Dr. Bandettini delves into the mysteries of the human brain. He is working to advance fMRI technology to parse out more information about the neural connections that are constantly and spontaneously active even when we think our minds are blank.

Ketamine is often thought of as an illicit party drug—something people take for a momentary high. But it wasn’t designed to be a mind-altering drug. Originally, ketamine was developed as anesthetic to relieve temporary pain. And now it seems the drug can provide solace not just from physical distress. At the NIH, Dr. Carlos Zarate is investigating how ketamine can rapidly reduce depressive symptoms in people with treatment-resistant depression or bipolar depression, for whom other options have not helped.

The success of mRNA vaccines against the coronavirus that causes COVID-19, has brought RNA biology into the limelight. Now, with the world's attention, what's next for this biomedical rising star? NIH scientists, Dr. Richard Maraia and Dr. Natasha Caplen, have long recognized the potential of RNA in improving human health. In this episode, they discuss the prospects of RNA biology and how their work could inform the future of RNA as an innovative class of medicine.

The neurons in our brains use both electrical and chemical signals to communicate. When those signals are not generated or interpreted correctly, serious problems can arise. Dr. Jerry Yakel is a neurobiologist studying acetylcholine receptors, which allow neurons to turn signals transmitted using the chemical acetylcholine into electrical messages. Because acetylcholine receptors are found on so many nerve cells, numerous neurological disorders can arise when they fail to work properly, including Alzheimer’s, Parkinson’s, and epilepsy. By studying these receptors, Dr. Yakel’s team hopes to better understand how they contribute to disease, which could eventually lead to therapies for a variety of neurological conditions.

Jerry Yakel, Ph.D., is a Senior Investigator in the Ion Channel Physiology Group at the NIH’s National Institute of Environmental Health Sciences (NIEHS). Learn more about Dr. Yakel and his research at https://irp.nih.gov/pi/jerrel-yakel

Centuries of selective breeding have given rise to a staggering variety of dog breeds, each with its own traits and behaviors. But shallow gene pools have also put some breeds at higher risk for disease. Dr. Elaine Ostrander runs the Dog Genome Project at the National Human Genome Research Institute. Her team includes Dr. Heidi Parker. Together, they are digging for clues to understand how genes code for dogs' diversity and disease. Clues that might also inform the health of their two-legged caregivers.

None of the groundbreaking research taking place in the IRP would be possible with the hard work and dedication of trainees. While they work to support the NIH’s mission to turn discovery into health, the Office of Intramural Training and Education (OITE) works to supports trainees in their professional pursuits. Dr. Sharon Milgram is the director of OITE and a strong proponent that good training begets good science. In this episode, she talks about the many ways OITE supports students and fellows so that they can achieve their best work and make the most of their experience in the IRP.

Pancreatic cancer kills more than 40,000 Americans each year, and just 6% of patients survive five years or more after diagnosis, because the disease metastasizes very early in its development and is resistant to most current treatments. Dr. Christine Alewine is a physician-scientist exploring new treatment strategies for pancreatic cancer. Her lab and clinic are testing and refining two recombinant immunotoxins that target a protein called mesothelin that is present on the surface of several types of cancer tumor cells, including pancreatic, ovarian, and some lung cancers. If clinical trials show that the drug is safe and effective, it could lead to much needed systemic therapies for these cancer patients.

Christine Campo Alewine, M.D., Ph.D., is an NIH Lasker Clinical Research Scholar and a Principal Investigator in the Laboratory of Molecular Biology at the NIH's National Cancer Institute (NCI) Center for Cancer Research (CCR). Learn more about Dr. Alewine and her research at https://irp.nih.gov/pi/christine-alewine

Small errors can quickly escalate to have large repercussions. When it comes to cancer, molecular changes to DNA can trigger chain reactions that cause cells to go awry and spread uncontrollably. Dr. Louis Staudt works to identify such changes, known as genetic mutations, and find ways to stop them from snowballing into a deadly disease. In this episode, Dr. Staudt recounts the story of how he differentiated subtypes of lymphomas to develop a treatment for patients as an early success of precision medicine.

Dr. Staudt is a principle investigator and the director of the Center for Cancer Genomics at the National Cancer Institute. He was recently elected into the National Academy of Medicine. Learn more about his research at https://irp.nih.gov/pi/louis-staudt.

Time and again, diversity and inclusion initiatives have proven to boost productivity and overall well-being in the workplace. But despite countless studies and although there have been significant strides in recent history, the struggle to ensure equal opportunity persists. At the NIH, the Scientific Workforce Diversity (SWD) Office is expanding recruitment and retention with Dr. Hannah Valantine as its first chief officer. She emphasizes how proper resources, mentorship, and community are essential for progress in the biomedical field.

Dr. Valantine is also a cardiologist and Senior Investigator of the Laboratory of Transplantation Genomics in the National Heart, Blood, and Lung Institute (NHLBI). Learn more about her research at https://irp.nih.gov/pi/hannah-valantine

This year has seen a record number of dengue cases all over the world. It might not be a fluke, as climate change expands the areas where the mosquito that transmits the tropical disease can thrive. New measures for treatment and protection are necessary, but there’s something peculiar about the way dengue infects the body that has stumped scientists for decades. That is, until now. Dr. Leah Katzelnick, Dr. Camila Odio and Dr. Stephen Whitehead from the National Institute of Allergy and Infectious Diseases (NIAID) are digging into dengue and coming up with ways to defy it.    

Our blood is made up of a diverse array of different cells, all of which originate from the same source: the ‘hematopoietic’ stem cells in our bone marrow. Dr. Cynthia Dunbar is a clinician working to understand how these stem cells grow, divide, and ultimately produce the cells that carry oxygen around the body and fight disease. Learning to safely transplant and manipulate hematopoietic stem cells could lead to treatments for a wide variety of diseases caused by a lack of properly functioning blood cells, including leukemia and aplastic anemia. 

Cynthia Dunbar, M.D., is a Principal Investigator in the Molecular Hematopoiesis Section at the NIH's National Heart, Lung, and Blood Institute (NHLBI). Learn more about Dr. Dunbar and her research at https://irp.nih.gov/pi/cynthia-dunbar

This episode features two legends of biomedical research. In the realm of human health and longevity, cancer’s ability to mutate, grow, and thwart the body’s natural defenses presents one of the greatest scientific challenges of our time. In 2001, Dr. Ira Pastan led the creation of a new type of cancer drug, a recombinant immunotoxin, that promised to directly target and kill cancer cells. After years of research and clinical trials, this first-generation immunotoxin was approved by the FDA in September 2018 for certain adults with hairy cell leukemia, providing a promising new therapy to a group of patients who previously had few other options.

And we have a special guest host for this episode, Dr. Michael Gottesman, who, as the NIH Deputy Director for Intramural Research, leads the thousands of researchers and clinicians working within the IRP each day — while also conducting groundbreaking research in his own laboratory into how cancer cells become resistant to chemotherapy and other anti-cancer drugs. Drs. Gottesman and Pastan are two guiding lights in our quest to overcome the obstacles to effectively treating cancer in order to improve and save potentially millions of lives. As friends and colleagues for many years, they also trained and collaborated with several of the most celebrated IRP researchers who made extraordinary breakthroughs for human health.

Pregnancy is by no means necessary for motherhood, but it is necessary for life. And it's no picnic. A pregnant person can experience complications like anemia, UTIs, hypertension, diabetes, and exhaustion. Maintaining maternal health during pregnancy can be challenging, but it is integral for the health of the fetus. Dr. Diana Bianchi is a physician-scientist and the director of the National Institute of Child Health and Human Development (NICHD), where she works to improve care for the mommy-baby unit.

Learn more about her research at https://irp.nih.gov/pi/diana-bianchi.

Beverly Gage came to the NIH with a condition that had never been observed before. A mysterious genetic mutation that caused her chronic joint pain and inflammation led her to Dr. Michael Ombrello, an expert in rare inflammatory diseases at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Where their paths cross shows us the current challenges of diagnosing, treating, and living with a disorder that is new to science.

Social distancing is the best way to curtail the spread of COVID-19, but if innumerable days of isolation start to feel like they’re taking a toll on your mental welfare, there might be some solace waiting in the kitchen. According to mental health experts, cooking can reduce anxiety and alleviate mental distress. Dr. Nicole Farmer is a clinical researcher studying many facets of how diet affects human biology and behavior, including the effects of cooking interventions on mental well-being.

Dr. Farmer is a staff scientist at the NIH Clinical Center and a 2020 recipient of the William G. Coleman Jr. Minority Health and Health Disparities Research Innovation Award from the National Institute of Minority Health and Health Disparities (NIMHD). Learn more about her research at https://www.nimhd.nih.gov/programs/intramural/research-award/2020-awardees/farmer.html

Dr. Dori Germolec is a biologist studying how the chemicals in our environment affect the immune system, including toxic or carcinogenic effects of molds and dietary supplements. From bisphenols and flame retardants to arsenic in the drinking water and polycyclic aromatic hydrocarbons, we are all exposed to a mixture of different compounds on a daily basis. Dr. Germolec’s research as part of the National Toxicology Program informs agencies like the EPA and FDA about the potential hazards of environmental toxins so that chemicals and substances can be properly regulated to keep people safe and healthy, both at home and in the workplace.

Dori Germolec, Ph.D., leads the Systems Toxicology Group of the NIH's National Institute of Environmental Health Sciences (NIEHS) National Toxicology Program (NTP). Learn more at: https://www.niehs.nih.gov/research/atniehs/labs/tob/systems/index.cfm

Our houses, workplaces, and even the air we breathe are teeming with microbes, some of which can cause severe illness. Dr. Catharine Bosio is an immunologist studying how airborne pathogens infect and alter cells in the lungs. Her work focuses in particular on a bacterium called Francisella tularensis, which causes a life-threatening disease called tularemia and has the unique ability to change how energy-producing mitochondria function in immune cells. Dr. Bosio's experiments with these deadly bacteria could lead to more effective ways to diagnose and treat tularemia and other infectious diseases.  

Catharine Bosio, Ph.D., is a Senior Investigator in the Immunity to Pulmonary Pathogens Section at the NIH's National Institute of Allergy and Infectious Diseases (NIAID). Learn more about Dr. Bosio and her research at https://irp.nih.gov/pi/catharine-bosio. 

For Dr. Steve Holland, the mystery of why some people are more prone to disease is as much a curiosity as it is a calling. Dr. Holland is the scientific director and chief of the immunopathogenesis section at the National Institute of Allergy and Infectious Diseases (NIAID) where he searches for signs to explain differences in susceptibility to certain infections. In this episode, he discusses how the immune system can thwart its own defenses by producing antibodies that block the chemical signals it needs to put up a fight.

Perhaps now more than ever, it is undeniable how integral vaccines have become to public health. Vaccines protect us from a whole host of infectious diseases, including chickenpox, measles and the seasonal flu. With a new threat at hand, scientists at the NIH swiftly developed a vaccine candidate against the novel coronavirus that causes COVID-19. The pre-clinical effort was driven in part by Dr. Kizzmekia Corbett. 

Dr. Corbett is a viral immunologist and research fellow in the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID). Learn more about the work taking place at the VRC at https://www.niaid.nih.gov/about/vrc

Science is receptive to new information that can refine the theories we use to make sense of the world. Such is the case with Dr. Lauren Porter, a Stadtman investigator at the National Library of Medicine who is helping redefine the way we understand how proteins behave. She is looking at a new class of proteins that can change their structure and function much like the famous Transformer robots that morph into different machines. Understanding how these proteins switch their shape could help scientists understand the molecular basis of certain diseases like cancer and Alzheimer’s.

Nutrition is a contentious topic. It’s hard to tell fact from fiction. One day eggs are good for you, the next they have too much fat. But what about the keto craze? Doesn’t it say you should eat mostly fats? Fortunately, there are scientist like Dr. Kevin Hall who are working to debunk the myths and give us the real skinny on how the foods we eat affect our health. Most recently, Dr. Hall published a study that put two well-known diets head-to-head to see which led people to consume more calories.

Sugars, also referred to as carbohydrates, aren’t just substances we add to make coffee taste less bitter or food sweeter; they are an entire class of molecules necessary for life. The study of these carbohydrates is called glycobiology. Dr. John Hanover is a glycobiologist and the chief of the laboratory of cell and molecular biology at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). His work is advancing scientists’ understanding of the sugar structures responsible for rare diseases and genetic transgenerational inheritance.

Historical failings, like the Chinese Exclusion Act of 1882 that restricted immigration from China for 61 years, have cast a shadow of prejudice and discrimination over Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations. Its effects continue to loom heavy, often reducing these groups to a single racial-ethnic category and masking major differences that exist between them, even when it comes to their health. In this episode, Devon Valera, from the Office of NIH History, breaks down how history has shaped AANHPI experiences and perceptions, and Dr. Jacqueline Vo from the National Cancer Institute (NCI), explains why science is now calling to dismantle the myth that these populations are a monolithic group.  

There is more to color than meets the eye. According to Dr. Bevil Conway, how we perceive color can inform how our brains receive, interpret, and generate knowledge about the world. Dr. Conway is a visual artist and a neuroscientist at the National Eye Institute. He is working to decode the neural basis of color. In a recent study, his lab mapped how different colors can stimulate different patterns of brain activity.

When the COVID-19 pandemic struck, racial and ethnic minority groups were disproportionately hit. The health inequities pulled at the seams of a system that was already frayed. Dr. Anna Nápoles works to close gaps in healthcare as the first Latina scientific director of the National Institute on Minority Health and Health Disparities (NIMHD). She is reducing the types of hurdles that once hindered her parents so that all populations can live long, healthy, and productive lives.

Learn more about Dr. Nápoles's research at https://irp.nih.gov/pi/anna-napoles.

Radioactive drugs carry radioactive substances that can be engineered to specifically target and kill tumor cells inside the body. In 2018, the FDA approved a radioactive drug called Lutathera to treat tumors that affect the pancreas or gastrointestinal tract. Now, scientists at the NIH led by Dr. Frank Lin are testing whether Lutathera can also be effective against rare tumors of the adrenal glands. Dr. Lin is a clinician and researcher focused on bringing radioactive drugs — also known as radionuclides — from bench to bedside. His work could accelerate the development of new therapies for patients with rare cancers who have few or no other treatment options.

Frank Lin, M.D., is a Lasker Clinical Research Scholar in the Center for Cancer Research at the NIH’s National Cancer Institute (NCI). Learn more about Dr. Lin and his research at https://irp.nih.gov/pi/frank-lin

Epidemiologists are the watchful guardians of public health. They collect and analyze data to track the status quo. When there are deviations, they crunch the numbers to understand who is getting sick, where, how, and why. Dr. Meredith Shiels is an epidemiologist and senior investigator at the National Cancer Institute (NCI) studying cancer mortality rates to discern what populations might be at higher risk, figure out ways to mitigate those risks, and evaluate whether those measures are working.  

Learn more about Dr. Shiels’s research at  https://irp.nih.gov/pi/meredith-shiels.

Despite negative consequences and the desire to stop, millions of people with compulsive behaviors can’t break the self-destructive cycles that disrupt their daily lives. Dr. Veronica Alvarez and Dr. Bruno Averbeck from the National Institute of Mental Health run the Center on Compulsive Behaviors (CCB) which brings together NIH scientists to understand what drives these repetitive and often detrimental behaviors. The CCB strives to decipher the neural circuitry that leads to compulsive behaviors in hopes of improving treatments and designing new interventions.

Learn more about the CCB at https://research.ninds.nih.gov/researchers/center-compulsive-behaviors-ccb.

The blood-brain barrier keeps bad actors like toxins, viruses, and bacteria from entering the brain. But in the case of brain cancer when the danger is already inside, the blood-brain barrier can work against a person’s health by shutting out the medications meant to eliminate the threat. Dr. Sadhana Jackson from the National Institute of Neurological Disorders and Stroke (NINDS) works to figure out ways to selectively get cancer treatments through the blood-brain barrier to treat patients with certain types of brain tumors known as gliomas.

Learn more about Dr. Jackson work at https://irp.nih.gov/pi/sadhana-jackson.

Anybody who observes a person with a neurological illness like Tourette syndrome or schizophrenia can clearly see how these conditions affect behavior. What’s much more difficult to determine is how these ailments relate to changes in the brain. Dr. Armin Raznahan is a child psychiatrist who uses a genetics-first approach and state-of-the-art neuroimaging tools to examine how the size and shape of the brain differ in children and adolescents with neuropsychiatric disorders compared to healthy individuals. His discoveries about these illnesses could ultimately improve our ability to identify and treat people who have them, as well as predict which children might develop them.

Armin Raznahan, M.D., Ph.D., is a Lasker Clinical Research Scholar in the Human Genetics Branch at the NIH’s National Institute of Mental Health (NIMH). Learn more about Dr. Raznahan and his research at https://irp.nih.gov/pi/armin-raznahan

In this episode, Dr. Richard Childs, a senior investigator and Clinical Director of the National Heart, Lung, and Blood Institute (NHLBI), recounts his experience using the antiviral remdesivir to treat patients with COVID-19 in one of the early hot zones of the pandemic. He led a team sent to care for passengers on the Diamond Princess cruise ship that was held in quarantine in Yokohama, Japan at the start of the outbreak. Since then, remdesivir has continued to gain traction as a possible standard of care. Dr. Matthew Hall, biology group leader at the National Center for Advancing Translational Sciences (NCATS), explains the development of the drug and its newfound purpose in the battle against the novel coronavirus.  

When people refer to the NIH as the “National Institutes of Hope,” Dr. Bill Gahl is one of the many people who come to mind. Dr. Gahl is a medical geneticist working to help patients with rare and undiagnosed diseases. His research group focuses on inborn errors of metabolism, which include defects in the body’s biochemical processes caused by rare genetic disorders, such as cystinosis, Hermansky-Pudlak syndrome, alkaptonuria, and ciliopathies.

Transcending biomedical boundaries to take advantage of the IRP’s unique team-science environment, Dr. Gahl led the creation of the NIH’s Undiagnosed Diseases Program to provide answers and possible treatments for people with mysterious conditions that have long eluded diagnosis. Since seeing their first patient at the NIH Clinical Center in July of 2008, the Program has expanded to become the Undiagnosed Diseases Network, which now includes 12 clinical sites along with supporting scientific facilities around the country. Even when no concrete answer or cure can be found, each patient shares new information that may in the future help other people facing similar health problems, and such hope can provide powerful meaning for people’s struggles that seem to occur without reason.

William Gahl, M.D., Ph.D., is a Senior Investigator in the Medical Genetics Branch of the NIH's National Human Genome Research Institute (NHGRI). Learn more about Dr. Gahl and his research at https://irp.nih.gov/pi/william-gahl

In nature, strategic alliances can mean the difference between life and death. For humans, such vital partnerships exist between us and the trillions of microbes we unwittingly host in and on our bodies - together called the microbiome. Dr. Heidi Kong uses genomics to uncover the microbe-host interactions taking place all over our skin. Building on her work and a growing understanding of the skin microbiome, Dr. Ian Myles has developed a bacterial spray that improves eczema, an inflammatory skin disease.

NASA recently unveiled the first images taken by the James Webb Telescope. But the distant cosmos aren't the only ones coming into focus. While astronomers point their instruments up to peer into the stars, microscopists like Dr. Hari Shroff are focusing their gaze down to capture life on Earth. As chief of the Section on High Resolution Optical Imaging at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Dr. Shroff engineers new microscopes to render the invisibly small in new and improved resolution.

The annual flu vaccine is the best way to prevent yourself and others from getting sick. But sometimes the antigens the vaccine trains your body to fight are not similar enough to the strains of influenza circulating that year. This mismatch allows viruses to fly under the radar and spread undetected. It's a problem scientists hope to solve with a universal flu vaccine. Dr. Matthew Memoli is an influenza expert at the National Institute of Allergy and Infectious Diseases (NIAID). He is preparing to test a new vaccine candidate that could offer protection from more flu strains and for more people.

This is Part 2 of our conversation with Dr. Dennis Drayna, a human geneticist who has identified mutations in several genes that cause communications disorders, particularly stuttering, using family- and population-based genetic methods. Dr. Drayna's team studies the biochemical and cellular effects of these mutations and how they may cause specific neuronal pathologies. With so much to cover, we divided this episode into two parts. Here, we continue to explore stuttering research and delve into Dr. Drayna’s perspectives about research and research training at the NIH, as well as his lab’s ground-breaking work on how genetic variation affects the sense of taste and how population-specific genetic factors can influence preference for menthol in cigarettes, a common flavor additive that is particularly popular among African American smokers.

Dennis Drayna, Ph.D., is a Senior Investigator in the Section on Systems Biology of Communication Disorders at NIH's National Institute on Deafness and Other Communication Disorders (NIDCD). Learn more about Dr. Drayna and his research at https://irp.nih.gov/pi/dennis-drayna

Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk. Dr. Nehal Mehta currently directs the largest ongoing cohort study to date in psoriasis, and his research is showing that local inflammation in different areas of the body such as the teeth, scalp, knees, skin, or gut has systemic consequences, and treating that local inflammation can help heal heart disease.

Nehal Mehta, M.D., M.S.C.E., F.A.H.A., is the inaugural NIH Lasker Clinical Research Scholar and a Principal Investigator in the Section of Inflammation and Cardiometabolic Diseases at the NIH's National Heart, Lung, and Blood Institute (NHLBI). Learn more about Dr. Mehta and his research at https://irp.nih.gov/pi/nehal-mehta

The average age for the start of puberty has been dropping for decades. It’s a global trend that could be signaling a public health threat to the physical and psychological development of younger, more vulnerable swaths of the population. Still, there’s no clear culprit for early puberty; it’s a complicated puzzle with many scattered pieces. At the National Institute of Environmental Health Sciences (NIEHS), pediatric neuroendocrinologist Dr. Natalie Shaw has been assembling the pieces together and recently found a new lead hiding in plain sight.

Dennis Drayna, Ph.D., is a human geneticist who has identified mutations in several genes that cause communications disorders, particularly stuttering. With so much to cover, we divided his episode into two parts. Here, in part 1, we discuss Dr. Drayna’s research into the genetics of stuttering, including the use of family- and population-based genetic methods. In part 2 to follow, we continue to explore stuttering research and delve into Dr. Drayna’s perspectives about research and research training at the NIH. We’ll also discuss his lab’s ground-breaking work on how genetic variation affects the sense of taste, and how population-specific genetic factors can influence preference for menthol in cigarettes, a common flavor additive that is particularly popular among African American smokers.

Dennis Drayna, Ph.D., is a Senior Investigator in the Section on Systems Biology of Communication Disorders at NIH's National Institute on Deafness and Other Communication Disorders (NIDCD). Learn more about Dr. Drayna and his research at https://irp.nih.gov/pi/dennis-drayna