14 Search Results for "ramirez"
All of Us Research Program Participants Fuel Both Scientific and Personal Discovery
Posted on by Josh Denny, M.D., M.S., All of Us Research Program
The NIH’s All of Us Research Program is a historic effort to create an unprecedented research resource that will speed biomedical breakthroughs, transform medicine and advance health equity. To create this resource, we are enrolling at least 1 million people who reflect the diversity of the United States.
At the program’s outset, we promised to make research a two-way street by returning health information to our participant partners. We are now delivering on that promise. We are returning personalized health-related DNA reports to participants who choose to receive them.
That includes me. I signed up to receive my “Medicine and Your DNA” and “Hereditary Disease Risk” reports along with nearly 200,000 other participant partners. I recently read my results, and they hit home, revealing an eye-opening connection between my personal and professional lives.
First, the professional. Before coming to All of Us, I was a practicing physician and researcher at Vanderbilt University, Nashville, TN, where I studied how a person’s genes might affect his or her response to medications. One of the drug-gene interactions that I found most interesting is related to clopidogrel, a drug commonly prescribed to keep arteries open after a major cardiovascular event, like a heart attack, stroke, or placement of a stent.
People with certain gene variations are not able to process this medication well, leaving them in a potentially risky situation. The patient and their health care provider may think the condition is being managed. But, since they can’t process the medication, the patient’s symptoms and risks are likely to increase.
The impact on patients has been seen in numerous studies, including one that I published with colleagues last year in the Journal of Stroke and Cerebrovascular Disease . We found that stroke risk is three times higher in patients who were poor responders to clopidogrel and treated with the drug following a “mini-stroke”—also known as a transient ischemic attack. Other studies have shown that major cardiovascular events were 50 percent more common in individuals who were poor responders to clopidogrel . Importantly, there are alternative therapies that work well for people with this genetic variant.
Now, the personal. Reading my health-related results, I learned that I carry some of these very same gene variations. So, if I ever needed a medicine to manage my risk of blood clots, clopidogrel would not likely work well for me.
Instead, should I ever need treatment, my provider and I could bypass this common first-line therapy and choose an alternate medicine. Getting the right treatment on the first try could cut my chances of a heart attack in half. The benefits of this knowledge don’t stop with me. By choosing to share my findings with family members who may have inherited the same genetic variations, they can discuss it with their health care teams.
Other program participants who choose to receive results will experience the same process of learning more about their health. Nearly all will get actionable information about how their body may process certain medications. A small percentage, 2 to 3 percent, may learn they’re at higher risk of developing several severe hereditary health conditions, such as certain preventable heart diseases and cancers. The program will provide a genetic counselor at no cost to all participants to discuss their results.
To enroll participants who reflect the country’s diverse population, All of Us partners with trusted community organizations around the country. Inclusion is vitally important in the field of genomics research, where available data have long originated mostly from people of European ancestry. In contrast, about 50 percent of the All of Us’ genomic data come from individuals who self-identify with a racial or ethnic minority group.
More than 3,600 research projects are already underway using data contributed by participants from diverse backgrounds. What’s especially exciting about this “ecosystem” of discovery between participants and researchers is that, by contributing their data, participants are helping researchers decode what our DNA is telling us about health across all types of conditions. In turn, those discoveries will deepen what participants can learn.
Those who have stepped up to join All of Us are the heartbeat of this historic research effort to advance personalized approaches in medicine. Their contributions are already fueling new discoveries in numerous areas of health.
At the same time, making good on our promises to our participant partners ensures that the knowledge gained doesn’t only accumulate in a database but is delivered back to participants to help advance their own health journeys. If you’re interested in joining All of Us, we welcome you to learn more.
 CYP2C19 loss-of-function is associated with increased risk of ischemic stroke after transient ischemic attack in intracranial atherosclerotic disease. Patel PD, Vimalathas P, Niu X, Shannon CN, Denny JC, Peterson JF, Chitale RV, Fusco MR. J Stroke Cerebrovasc Dis. 2021 Feb;30(2):105464.
 Predicting clopidogrel response using DNA samples linked to an electronic health record. Delaney JT, Ramirez AH, Bowton E, Pulley JM, Basford MA, Schildcrout JS, Shi Y, Zink R, Oetjens M, Xu H, Cleator JH, Jahangir E, Ritchie MD, Masys DR, Roden DM, Crawford DC, Denny JC. Clin Pharmacol Ther. 2012 Feb;91(2):257-263.
Join All of Us (All of Us/NIH)
NIH’s All of Us Research Program returns genetic health-related results to participants, NIH News Release, December 13, 2022.
NIH’s All of Us Research Program Releases First Genomic Dataset of Nearly 100,000 Whole Genome Sequences, NIH News Release, March 17, 2022.
Funding and Program Partners (All of Us)
Medicine and Your DNA (All of Us)
Clopidogrel Response (National Library of Medicine/NIH)
Hereditary Disease Risk (All of Us)
Preparing for DNA Results: What Is a Genetic Counselor? (All of Us)
Research Projects Directory (All of Us)
Note: Dr. Lawrence Tabak, who performs the duties of the NIH Director, has asked the heads of NIH’s Institutes, Centers, and Offices to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 24th in the series of NIH guest posts that will run until a new permanent NIH director is in place.
The Amazing Brain: Seeing Two Memories at Once
Posted on by Lawrence Tabak, D.D.S., Ph.D.
The NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative is revolutionizing our understanding of the human brain. As described in the initiative’s name, the development of innovative imaging technologies will enable researchers to see the brain in new and increasingly dynamic ways. Each year, the initiative celebrates some standout and especially creative examples of such advances in the “Show Us Your BRAINs! Photo & Video Contest. During most of August, I’ll share some of the most eye-catching developments in our blog series, The Amazing Brain.
In this fascinating image, you’re seeing two stored memories, which scientists call engrams, in the hippocampus region of a mouse’s brain. The engrams show the neural intersection of a good memory (green) and a bad memory (pink). You can also see the nuclei of many neurons (blue), including nearby neurons not involved in the memory formation.
This award-winning image was produced by Stephanie Grella in the lab of NIH-supported neuroscientist Steve Ramirez, Boston University, MA. It’s also not the first time that the blog has featured Grella’s technical artistry. Grella, who will soon launch her own lab at Loyola University, Chicago, previously captured what a single memory looks like.
To capture two memories at once, Grella relied on a technology known as optogenetics. This powerful method allows researchers to genetically engineer neurons and selectively activate them in laboratory mice using blue light. In this case, Grella used a harmless virus to label neurons involved in recording a positive experience with a light-sensitive molecule, known as an opsin. Another molecular label was used to make those same cells appear green when activated.
After any new memory is formed, there’s a period of up to about 24 hours during which the memory is malleable. Then, the memory tends to stabilize. But with each retrieval, the memory can be modified as it restabilizes, a process known as memory reconsolidation.
Grella and team decided to try to use memory reconsolidation to their advantage to neutralize an existing fear. To do this, they placed their mice in an environment that had previously startled them. When a mouse was retrieving a fearful memory (pink), the researchers activated with light associated with the positive memory (green), which for these particular mice consisted of positive interactions with other mice. The aim was to override or disrupt the fearful memory.
As shown by the green all throughout the image, the experiment worked. While the mice still showed some traces of the fearful memory (pink), Grella explained that the specific cells that were the focus of her study shifted to the positive memory (green).
What’s perhaps even more telling is that the evidence suggests the mice didn’t just trade one memory for another. Rather, it appears that activating a positive memory actually suppressed or neutralized the animal’s fearful memory. The hope is that this approach might one day inspire methods to help people overcome negative and unwanted memories, such as those that play a role in post-traumatic stress disorder (PTSD) and other mental health issues.
Stephanie Grella (Boston University, MA)
Ramirez Group (Boston University)
Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)
Show Us Your BRAINs Photo & Video Contest (BRAIN Initiative)
NIH Support: BRAIN Initiative; Common Fund
Unraveling the Role of the Skin Microbiome in Health and Disease
Posted on by Lindsey A. Criswell, M.D., M.P.H., D.Sc., National Institute of Arthritis and Musculoskeletal and Skin Diseases
Human skin is home to diverse ecosystems including bacteria, viruses, and fungi. These microbial communities comprise hundreds of species and are collectively known as the skin microbiome. The skin microbiome is thought to play a vital role in fending off disease-causing microorganisms (pathogens), boosting barrier protection, and aiding immune defenses.
Maintaining a balanced skin microbiome involves a complex and dynamic interplay among microorganisms, immune cells, skin cells, and other factors. In general, bacteria far outnumber viral, fungal, or other microbial species on the skin. Bacterial communities, which are strongly influenced by conditions such as skin moisture, temperature, and pH, vary widely across the body. For example, facial cheek skin hosts mostly Cutibacterium along with a bit of the skin fungus Malassezia. The heel is colonized by different types of bacteria including Staphylococcus and Corynebacteria.
In some diseases, such as acne and eczema, the skin microbiome is altered. Typically, this means an increase in pathogenic microorganisms and a decrease in beneficial ones. An altered skin microbiome can also be associated with inflammation, severe disease symptoms, and changes in the human immune system.
Heidi H. Kong is working to understand the role of the skin microbiome in health and disease. She is a senior investigator in the Intramural Research Program at NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and an adjunct investigator at NIH’s National Cancer Institute (NCI).
More than a decade ago, Kong and Julie A. Segre, an intramural researcher at NIH’s National Human Genome Research Institute, analyzed the microbial makeup of healthy individuals. Kong swabbed the skin of these healthy volunteers in 20 different sites, from the forehead to the toenail. The study revealed that the surface of the human body provides various environmental niches, depending on whether the skin is moist, dry, or sebaceous (oily). Different bacterial species predominate in each niche. Kong and Segre were particularly interested in body areas that have predilections for disease. For example, psoriasis is often found on the outside of elbows and knees, and the back of the scalp.
Earlier this year, Kong and Segre published another broad analysis of the human skin microbiome  in collaboration with scientists at the European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), United Kingdom. This new catalog, called the Skin Microbial Genome Collection, is thought to identify about 85 percent of the microorganisms present on healthy skin from 19 body sites. It documents more than 600 bacterial species—including 174 that were discovered during the study—as well as more than 6,900 viruses and some fungi, including three newly discovered species.
Kong’s work has provided compelling evidence that the human immune system plays a role in shaping the skin microbiome. In 2018, she, Segre, and colleagues from the intramural programs of NCI and NIH’s National Institute of Allergy and Infectious Diseases analyzed skin from eight different sites on 27 people with a rare primary immunodeficiency disease known as DOCK8 deficiency .
People with the condition have recurrent infections in the skin, sinuses, and airways, and are susceptible to different cancers. Kong and colleagues found that the skin of people with DOCK8 deficiency contains significantly more DNA viruses (90 percent of the skin microbiome on average) than people without the condition (6 or 7 percent of the skin microbiome).
Other researchers are hoping to leverage features of the microbiome to develop targeted therapies for skin diseases. Richard L. Gallo, a NIAMS grantee at the University of California, San Diego, is currently focused on acne and eczema (also called atopic dermatitis). Acne is associated with certain strains of Cutibacterium acnes (C. acnes, formerly called Propionibacterium acnes or P. acnes). Eczema is often associated with Staphylococcus aureus (S. aureus).
Severe cases of acne and eczema are commonly treated with broad-spectrum antibiotics, which wipe out most of the bacteria, including beneficial species. The goal of microbiome-targeted therapy is to kill only the disease-associated bacteria and avoid increasing the risk that some strains will develop antibiotic resistance.
In 2020, Gallo and colleagues identified a strain of Staphylococcus capitis from healthy human skin (S. capitis E12) that selectively inhibits the growth of C. acnes without negatively impacting other bacteria or human skin cells . S. capitis E12 produces four different toxins that act together to target C. acnes. The research team created an extract of the four toxins and tested it using animal models. In most cases, the extract was more potent at killing C. acnes—including acne-associated strains—than several commonly prescribed antibiotics (erythromycin, tetracycline, and clindamycin). And, unlike antibiotics, the extract does not appear to promote drug-resistance, at least for the 20 generations observed by the researchers.
Eczema is a chronic, relapsing disease characterized by skin that is dry, itchy, inflamed, and prone to infection, including by pathogens such as S. aureus and herpes virus. Although the cause of eczema is unknown, the condition is associated with human genetic mutations, disruption of the skin’s barrier, inflammation-triggering allergens, and imbalances in the skin microbiome.
In 2017, Gallo’s research team discovered that, in healthy human skin, certain strains of Staphylococcus hominis and Staphylococcus epidermis produce potent antimicrobial molecules known as lantibiotics . These beneficial strains are far less common on the skin of people with eczema. The lantibiotics work synergistically with LL-37, an antimicrobial molecule produced by the human immune system, to selectively kill S. aureus, including methicillin-resistant strains (MRSA).
Gallo and his colleagues then examined the safety and therapeutic potential of these beneficial strains isolated from the human skin microbiome. In animal tests, strains of S. hominis and S. epidermis that produce lantibiotics killed S. aureus and blocked production of its toxin.
Gallo’s group has now expanded their work to early studies in humans. In 2021, two independent phase 1 clinical trials [5,6] conducted by Gallo and his colleagues investigated the effects of these strains on people with eczema. These double-blind, placebo-controlled trials involved one-week of topical application of beneficial bacteria to the forearm of adults with S. aureus-positive eczema. The results demonstrated that the treatment was safe, showed a significant decrease in S. aureus, and improved eczema symptoms in most patients. This is encouraging news for those hoping to develop microbiome-targeted therapy for inflammatory skin diseases.
As research on the skin microbiome advances on different fronts, it will provide deeper insight into the multi-faceted microbial communities that are so critical to health and disease. One day, we may even be able to harness the microbiome as a source of therapeutics to alleviate inflammation, promote wound healing, or suppress certain skin cancers.
 Integrating cultivation and metagenomics for a multi-kingdom view of skin microbiome diversity and functions. Saheb Kashaf S, Proctor DM, Deming C, Saary P, Hölzer M; NISC Comparative Sequencing Program, Taylor ME, Kong HH, Segre JA, Almeida A, Finn RD. Nat Microbiol. 2022 Jan;7(1):169-179.
 Expanded skin virome in DOCK8-deficient patients. Tirosh O, Conlan S, Deming C, Lee-Lin SQ, Huang X; NISC Comparative Sequencing Program, Su HC, Freeman AF, Segre JA, Kong HH. Nat Med. 2018 Dec;24(12):1815-1821.
 Identification of a human skin commensal bacterium that selectively kills Cutibacterium acnes. O’Neill AM, Nakatsuji T, Hayachi A, Williams MR, Mills RH, Gonzalez DJ, Gallo RL. J Invest Dermatol. 2020 Aug;140(8):1619-1628.e2.
 Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, Shafiq F, Kotol PF, Bouslimani A, Melnik AV, Latif H, Kim JN, Lockhart A, Artis K, David G, Taylor P, Streib J, Dorrestein PC, Grier A, Gill SR, Zengler K, Hata TR, Leung DY, Gallo RL. Sci Transl Med. 2017 Feb 22;9(378):eaah4680.
 Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nakatsuji T, Hata TR, Tong Y, Cheng JY, Shafiq F, Butcher AM, Salem SS, Brinton SL, Rudman Spergel AK, Johnson K, Jepson B, Calatroni A, David G, Ramirez-Gama M, Taylor P, Leung DYM, Gallo RL. Nat Med. 2021 Apr;27(4):700-709.
 Use of autologous bacteriotherapy to treat Staphylococcus aureus in patients with atopic dermatitis: A randomized double-blind clinical trial. Nakatsuji T, Gallo RL, Shafiq F, Tong Y, Chun K, Butcher AM, Cheng JY, Hata TR. JAMA Dermatol. 2021 Jun 16;157(8):978-82.
Acne (National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH)
Atopic Dermatitis (NIAMS)
Cutaneous Microbiome and Inflammation Laboratory, Heidi Kong (NIAMS)
Julie Segre (National Human Genome Research Institute/NIH)
Gallo Lab (University of California, San Diego)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the cool science that they support and conduct. This is the fifth in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]
Preventing Glaucoma Vision Loss with ‘Big Data’
Posted on by Dr. Francis Collins
Each morning, more than 2 million Americans start their rise-and-shine routine by remembering to take their eye drops. The drops treat their open-angle glaucoma, the most-common form of the disease, caused by obstructed drainage of fluid where the eye’s cornea and iris meet. The slow drainage increases fluid pressure at the front of the eye. Meanwhile, at the back of the eye, fluid pushes on the optic nerve, causing its bundled fibers to fray and leading to gradual loss of side vision.
For many, the eye drops help to lower intraocular pressure and prevent vision loss. But for others, the drops aren’t sufficient and their intraocular pressure remains high. Such people will need next-level care, possibly including eye surgery, to reopen the clogged drainage ducts and slow this disease that disproportionately affects older adults and African Americans over age 40.
Sally Baxter, a physician-scientist with expertise in ophthalmology at the University of California, San Diego (UCSD), wants to learn how to predict who is at greatest risk for serious vision loss from open-angle and other forms of glaucoma. That way, they can receive more aggressive early care to protect their vision from this second-leading cause of blindness in the U.S..
To pursue this challenging research goal, Baxter has received a 2020 NIH Director’s Early Independence Award. Her research will build on the clinical observation that people with glaucoma frequently battle other chronic health problems, such as high blood pressure, diabetes, and heart disease. To learn more about how these and other chronic health conditions might influence glaucoma outcomes, Baxter has begun mining a rich source of data: electronic health records (EHRs).
In an earlier study of patients at UCSD, Baxter showed that EHR data helped to predict which people would need glaucoma surgery within the next six months . The finding suggested that the EHR, especially information on a patient’s blood pressure and medications, could predict the risk for worsening glaucoma.
In her NIH-supported work, she’s already extended this earlier “Big Data” finding by analyzing data from more than 1,200 people with glaucoma who participate in NIH’s All of Us Research Program . With consent from the participants, Baxter used their EHRs to train a computer to find telltale patterns within the data and then predict with 80 to 99 percent accuracy who would later require eye surgery.
The findings confirm that machine learning approaches and EHR data can indeed help in managing people with glaucoma. That’s true even when the EHR data don’t contain any information specific to a person’s eye health.
In fact, the work of Baxter and other groups have pointed to an especially important role for blood pressure in shaping glaucoma outcomes. Hoping to explore this lead further with the support of her Early Independence Award, Baxter also will enroll patients in a study to test whether blood-pressure monitoring smart watches can add important predictive information on glaucoma progression. By combining round-the-clock blood pressure data with EHR data, she hopes to predict glaucoma progression with even greater precision. She’s also exploring innovative ways to track whether people with glaucoma use their eye drops as prescribed, which is another important predictor of the risk of irreversible vision loss .
Glaucoma research continues to undergo great progress. This progress ranges from basic research to the development of new treatments and high-resolution imaging technologies to improve diagnostics. But Baxter’s quest to develop practical clinical tools hold great promise, too, and hopefully will help one day to protect the vision of millions of people with glaucoma around the world.
 Machine learning-based predictive modeling of surgical intervention in glaucoma using systemic data from electronic health records. Baxter SL, Marks C, Kuo TT, Ohno-Machado L, Weinreb RN. Am J Ophthalmol. 2019 Dec; 208:30-40.
 Predictive analytics for glaucoma using data from the All of Us Research Program. Baxter SL, Saseendrakumar BR, Paul P, Kim J, Bonomi L, Kuo TT, Loperena R, Ratsimbazafy F, Boerwinkle E, Cicek M, Clark CR, Cohn E, Gebo K, Mayo K, Mockrin S, Schully SD, Ramirez A, Ohno-Machado L; All of Us Research Program Investigators. Am J Ophthalmol. 2021 Jul;227:74-86.
 Smart electronic eyedrop bottle for unobtrusive monitoring of glaucoma medication adherence. Aguilar-Rivera M, Erudaitius DT, Wu VM, Tantiongloc JC, Kang DY, Coleman TP, Baxter SL, Weinreb RN. Sensors (Basel). 2020 Apr 30;20(9):2570.
Glaucoma (National Eye Institute/NIH)
All of Us Research Program (NIH)
Video: Sally Baxter (All of Us Research Program)
Sally Baxter (University of California San Diego)
Baxter Project Information (NIH RePORTER)
NIH Director’s Early Independence Award (Common Fund)
NIH Support: Common Fund
Taking a Closer Look at COVID-19’s Effects on the Brain
Posted on by Dr. Francis Collins
While primarily a respiratory disease, COVID-19 can also lead to neurological problems. The first of these symptoms might be the loss of smell and taste, while some people also may later battle headaches, debilitating fatigue, and trouble thinking clearly, sometimes referred to as “brain fog.” All of these symptoms have researchers wondering how exactly the coronavirus that causes COVID-19, SARS-CoV-2, affects the human brain.
In search of clues, researchers at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) have now conducted the first in-depth examinations of human brain tissue samples from people who died after contracting COVID-19. Their findings, published in the New England Journal of Medicine, suggest that COVID-19’s many neurological symptoms are likely explained by the body’s widespread inflammatory response to infection and associated blood vessel injury—not by infection of the brain tissue itself .
The NIH team, led by Avindra Nath, used a high-powered magnetic resonance imaging (MRI) scanner (up to 10 times as sensitive as a typical MRI) to examine postmortem brain tissue from 19 patients. They ranged in age from 5 to 73, and some had preexisting conditions, such as diabetes, obesity, and cardiovascular disease.
The team focused on the brain’s olfactory bulb that controls our ability to smell and the brainstem, which regulates breathing and heart rate. Based on earlier evidence, both areas are thought to be highly susceptible to COVID-19.
Indeed, the MRI images revealed in both regions an unusual number of bright spots, a sign of inflammation. They also showed dark spots, which indicate bleeding. A closer look at the bright spots showed that tiny blood vessels in those areas were thinner than normal and, in some cases, leaked blood proteins into the brain. This leakage appeared to trigger an immune reaction that included T cells from the blood and the brain’s scavenging microglia. The dark spots showed a different pattern, with leaky vessels and clots but no evidence of an immune reaction.
While those findings are certainly interesting, perhaps equally noteworthy is what Nath and colleagues didn’t see in those samples. They could find no evidence in the brain tissue samples that SARS-CoV-2 had invaded the brain tissue. In fact, several methods to detect genetic material or proteins from the virus all turned up empty.
The findings are especially intriguing because there has been some suggestion based on studies in mice that SARS-CoV-2 might cross the blood-brain barrier and invade the brain. Indeed, a recent report by NIH-funded researchers in Nature Neuroscience showed that the viral spike protein, when injected into mice, readily entered the brain along with many other organs .
Another recent report in the Journal of Experimental Medicine, which used mouse and human brain tissue, suggests that SARS-CoV-2 may indeed directly infect the central nervous system, including the brain . In autopsies of three people who died from complications of COVID-19, the NIH-supported researchers detected signs of SARS-CoV-2 in neurons in the brain’s cerebral cortex. This work was done using the microscopy-based technique of immunohistochemistry, which uses antibodies to bind to a target, in this case, the virus’s spike protein. Also last month, in a study published in the journal Neurobiology of Disease, another NIH-supported team demonstrated in a series of experiments in cell culture that the SARS-CoV-2 spike protein could cross a 3D model of the blood-brain barrier and infect the endothelial cells that line blood vessels in the brain .
Clearly, more research is needed, and NIH’s National Institute of Neurological Disorders and Stroke has just launched the COVID-19 Neuro Databank/Biobank (NeuroCOVID) to collect more clinical information, primarily about COVID-19-related neurological symptoms, complications, and outcomes. Meanwhile, Nath and colleagues continue to explore how COVID-19 affects the brain and triggers the neurological symptoms often seen in people with COVID-19. As we learn more about the many ways COVID-19 wreaks havoc on the body, understanding the neurological symptoms will be critical in helping people, including the so-called Long Haulers bounce back from this terrible viral infection.
 Microvascular Injury in the Brains of Patients with Covid-19. Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. N Engl J Med. 2020 Dec 30.
 The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Rhea EM, Logsdon AF, Hansen KM, Williams LM, Reed MJ, Baumann KK, Holden SJ, Raber J, Banks WA, Erickson MA. Nat Neurosci. 2020 Dec 16.
 Neuroinvasion of SARS-CoV-2 in human and mouse brain. Song E, Zhang C, Israelow B, et al. J Exp Med (2021) 218 (3): e20202135.
 The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA, Razmpour R, Hale JF, Galie PA, Potula R, Andrews AM, Ramirez SH. Neurobiol Dis. 2020 Dec;146:105131.
COVID-19 Research (NIH)
Avindra Nath (National Institute of Neurological Disorders and Stroke/NIH)
NIH Support: National Institute of Neurological Disorders and Stroke; National Institute on Aging; National Institute of General Medical Sciences; National Cancer Institute; National Institute of Mental Health