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Reflecting on Two Years of Discovery and Looking Ahead to New NIH Leadership

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Lawrence Tabak in his office
Dr. Larry Tabak in his office at the National Institutes of Health. Credit: NIH

As I transition from my role as the Acting NIH Director, I’d like to thank you, the readers, for visiting the NIH Director’s Blog ever since I took the helm 22 months ago. From Long COVID to the opioid overdose epidemic to Alzheimer’s disease—we’ve covered a range of diseases and conditions, scientific advances, and programs. You were able to read about such a broad spectrum of science thanks in large part to the many Institute Directors at NIH who authored guest posts. I hope the blog has helped you learn more about what NIH does and the many ways that biomedical research impacts human health.

A key focus of my career as both a scientific investigator and administrative leader has been supporting trainees and finding new ways to cultivate and expand the next generation of researchers. In my many discussions with young investigators, I’ve often reminded them that they should not be afraid to fail. To the students and early-stage scientists who have visited this site: I hope these stories of discovery—often the result of earlier failures—have provided some insight and inspiration as you move through your scientific career or consider starting one.

I’d also like to thank the many people—employees, government and private partners, patients, scientists, advocates, and other members of the public—who have reached out with messages of support, and sometimes with messages of criticism. Both have helped inform the decisions I needed to make to fulfill the NIH mission.

In closing, I congratulate Dr. Monica Bertagnolli as she takes the helm as the next permanent NIH director. Dr. Bertagnolli—an outstanding physician scientist—is a strong leader who will bring fresh, bold new ideas to NIH and the biomedical research enterprise. I know she’ll be in good hands thanks to the outstanding staff across NIH and the leadership in the Department of Health and Human Services. I look forward to supporting her efforts and continuing to ensure that NIH research optimizes health for all people.

Can Bioprinted Skin Substitutes Replace Traditional Grafts for Treating Burn Injuries and Other Serious Skin Wounds?

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Three syringes filled with mixes of cell types are connected to a machine that is printing a disk of artificial skin. One prints a hypodermis layer, the next prints a dermis layer, and last an epidermis layer is printed.
Artificial skin is printed by layering specific cell mixtures to mimic human skin: epidermis (top), dermis (middle) and hypodermis (bottom). Credit: Donny Bliss/NIH

Each year in the U.S., more than 500,000 people receive treatment for burn injuries and other serious skin wounds.1 To close the most severe wounds with less scarring, doctors often must surgically remove skin from one part of a person’s body and use it to patch the injured site. However, this is an intensive process, and some burn patients with extensive skin loss do not have sufficient skin available for grafting. Scientists have been exploring ways to repair these serious skin wounds without skin graft surgery.

An NIH-funded team recently showed that bioprinted skin substitutes may serve as a promising alternative to traditional skin grafts in preclinical studies reported in Science Translational Medicine.2 The approach involves a portable skin bioprinter system that deposits multiple layers of skin directly into a wound. The recent findings add to evidence that bioprinting technology can successfully regenerate human-like skin to allow healing. While this approach has yet to be tested in people, it confirms that such technologies already can produce skin constructs with the complex structures and multiple cell types present in healthy human skin.

This latest work comes from a team led by Adam Jorgensen and Anthony Atala at Wake Forest School of Medicine’s Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC. Members of the Atala lab and their colleagues had earlier shown it was possible to isolate two major skin cell types found in the skin’s outer (epidermis) and middle (dermis) layers from a small biopsy of healthy skin, expand the number of cells in the lab and then deliver the cells directly into an injury using a specially designed bioprinter.3 Using integrated imaging technology to scan a wound, computer software “prints” cells right into an injury, mimicking two of our skin’s three natural layers.

In the new study, Atala’s team has gone even further to construct skin substitutes that mimic the structure of human skin and that include six primary human skin cell types. They then used their bioprinter to produce skin constructs with all three layers found in healthy human skin: epidermis, dermis, and hypodermis.

To put their skin substitutes to the test, they first transplanted them into mice. Their studies showed that the bioprinted skin encouraged the rapid growth of new blood vessels and had other features of normal-looking, healthy skin. The researchers were able to confirm that their bioprinted skin implants successfully integrated into the animals’ regenerated skin to speed healing.

Studies in a pig model of wound healing added to evidence that such bioprinted implants can successfully repair full-thickness wounds, meaning those that extend through all three layers of skin. The bioprinted skin patches allowed for improved wound healing with less scarring. They also found that the bioprinted grafts encouraged activity in the skin from genes known to play important roles in wound healing.

It’s not yet clear if this approach will work as well in the clinic as it does in the lab. To make it feasible, the researchers note there’s a need for improved approaches to isolating and expanding the needed skin cell types. Nevertheless, these advances come as encouraging evidence that bioprinted skin substitutes could one day offer a promising alternative to traditional skin grafts with the capacity to help even more people with severe burns or other wounds.


[1] Burn Incidence Fact Sheet. American Burn Association

[2] AM Jorgensen, et al. Multicellular bioprinted skin facilitates human-like skin architecture in vivoScience Translational Medicine DOI: 10.1126/scitranslmed.adf7547 (2023).

[3] M Albanna, et al. In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds. Scientific Reports DOI: 10.1038/s41598-018-38366-w (2019).

NIH Support: National Institute of Arthritis and Musculoskeletal and Skin Diseases

Words Matter, Actions Have Impact: Updating the NIH Mission Statement

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Cartoon of scientists working with DNA, microscopes and data, leading to two doctors talking with a patient who is in a wheelchair.
Credit: Donny Bliss, NIH

I’ve previously written and spoken about how diverse perspectives are essential to innovation and scientific advancement.1 Scientists and experts with different backgrounds and lived experiences can offer diverse and creative solutions to solve complex problems. We’re taking steps to create a culture within the biomedical and behavioral research enterprise of inclusion, equity, and respect for every member of society. We are also working to strengthen our efforts to include populations in research that have not been historically included or equitably treated.

As part of our effort to ensure that all people are included in NIH research, we’re updating our mission statement to reflect better the spirit of the agency’s work to optimize health for all people. The proposed, new statement is as follows:

“To seek fundamental knowledge about the nature and behavior of living systems and to apply that knowledge to optimize health and prevent or reduce illness for all people.”

Recently, we asked a team of subject matter experts to form a subgroup of the Advisory Committee to the Director’s Working Group on Diversity to advise NIH on how we can support the inclusion of people with disabilities in the scientific workforce and in the research enterprise. One of the subgroup’s recommendations was to update the current NIH mission statement to remove “reducing disability.” The subgroup explained that this language could be interpreted as perpetuating ableist beliefs that people with disabilities are flawed and need to be “fixed.”

Disability is often viewed solely as a medical problem requiring a cure or correction. However, this view can be stigmatizing as it focuses only on a perceived flaw in the individual. It does not account for how people identify and view themselves. It also does not account for the ways that society can be unaccommodating for people with disabilities.2,3 It’s important that we recognize the varied, nuanced and complex lived experiences among people with disabilities, many of whom may also face additional barriers as members of racial, ethnic, sexual and gender minority groups, people with lower incomes, and people who live in rural communities that are medically underserved.

Some of you may recall that we updated our mission statement in 2013 to remove phrasing that implied disability was a burden, since many people do not find their disabilities to be burdensome. As we re-examine our mission statement again in 2023, I’m reminded that strengthening diversity, equity, inclusion and accessibility (DEIA) is an ongoing process requiring our sustained engagement.

The input we’ve received has made it clear that words matter—language can perpetuate prejudices and implicit attitudes, which in turn can affect people’s behavior. We also acknowledge that it is time for the agency to review and consider how the words of our mission statement may affect the direction of our science.

In response, we are seeking the public’s input on the proposed, revised statement to ensure that it reflects the NIH mission as accurately as possible. The NIH mission should be inclusive of those who conduct research, those who participate in research, and those we serve—the American public. Anyone interested in providing feedback can send it to this submission website through Nov. 24, 2023.

We are grateful for the subgroup’s work and appreciate their time examining this issue in depth. I also want to recognize the helpful feedback that we’ve received from the disability community within NIH through the years, including recent listening sessions that helped guide the development of NIH’s DEIA Strategic Plan.

Going beyond the scientific workforce, both the Strategic Plan and the subgroup’s report recognize the importance of research on health disparities. People with disabilities often experience health conditions leading to poorer health and face discrimination, inequality and structural barriers that inhibit access to health care, resulting in poorer health outcomes. NIH recently designated people with disabilities as a population with health disparities to encourage research specific to the health issues and unmet health needs of the disability community. NIH also issued a funding opportunity calling for research applications that address the intersecting impact of disability, race, ethnicity, and socioeconomic status on healthcare access and health outcomes.

The subgroup provided additional recommendations that we’re in the process of reviewing. We know one of our key challenges is data gathering that would give us a better snapshot of the workforce and the research we support. According to the CDC, 1 in 4 adults in the United States have a disability. However, in 2022 only 1.3% of principal investigators on NIH research grant applications and awards self-reported a disability. In 2022, 8.6% of the NIH workforce reported having a disability; however, I recognize that this is likely not reflective of the true percentage. We know that some people do not want to self-disclose for numerous reasons, including the fear of discrimination.

We hope that, in part, changing the mission statement would be a step in the right direction of changing the culture at NIH and the larger biomedical and behavioral research enterprise. I know that our efforts have sometimes fallen short, but we will continually work to foster a culture of inclusive excellence where people with disabilities and all people feel like they truly belong and are embraced as an asset to the NIH mission.


[1] MA Bernard et al. The US National Institutes of Health approach to inclusive excellence. Nature Medicine DOI:10.1038/s41591-021-01532-1 (2021)

[2] DS Dunn & EE Andrews. Person-first and identity-first language: Developing psychologists’ cultural competence using disability language The American Psychologist DOI: 10.1037/a0038636 (2015)

[3] International Classification of Functioning, Disability and Health (2002) Towards a Common Language for Functioning, Disability and Health. World Health Organization


ACD Working Group on Diversity, Subgroup on Individuals with Disabilities, NIH

Advisory Committee to the Director Working Group on Diversity Subgroup on Individuals with Disabilities: Report, NIH

Request for Information: Inviting Comments and Suggestions on Updating the NIH Mission Statement, NIH

NIH designates people with disabilities as a population with health disparities, Sept. 26, 2023, NIH News Releases

NIH-Wide Strategic Plan for Diversity, Equity, Inclusion, and Accessibility (DEIA), NIH

Disability and Health Overview, CDC

Data on Researchers’ Self-Reported Disability Status, NIH Office Of Extramural Research

Total NIH Workforce Demographics for Fiscal Year 2022 Fourth Quarter, NIH Office of Equity, Diversity, and Inclusion

Revolutionizing Technology to Treat Genetic Diseases: The NIH TARGETED Challenge

Posted on by Lawrence Tabak, D.D.S., Ph.D. and Douglas M. Sheeley, Sc.D., NIH Common Fund

Targeted (Targeted Genome Editor Delivery) Challenge. A strand of DNA with a number of glowing base pairs being targeted with an arrow

Recent scientific advances in the field of genome editing, which enables precise modifications to DNA, have greatly increased the potential to treat genetic diseases. Despite revolutionary progress in this area, treatment options remain limited. Several scientific challenges must be addressed before gene editing can be widely used in the clinic. For example, gene editing tools may cut in unintended areas in addition to the target site, and more research is necessary to understand how these errors affect patients.

Another key challenge is that many organs remain difficult to reach with gene therapies because we do not have adequate ways to deliver gene editing tools to all cells. While efficient delivery technologies exist for some targets, like liver cells, novel and specialized delivery methods designed for specific cell types and locations in the body are needed to ensure genome editing tools can reach sufficient numbers and types of somatic cells to modify DNA safely and effectively. Somatic cell gene therapies target non-reproductive cells, so the changes only affect the person who receives the gene therapy and are not passed down generation to generation.

To address these challenges, NIH launched the TARGETED (Targeted Genome Editor Delivery) Challenge, a multi-phase competition funded through the NIH Common Fund as part of the NIH Somatic Cell Genome Editing (SCGE) Program. SCGE was funded in 2018 to improve the efficacy and specificity of genome editing to help reduce the burden of common and rare diseases caused by genetic changes.

As part of the TARGETED Challenge, research teams will develop technologies for delivering genome editors to somatic cells. NIH will award up to $6 million in prize money across the challenge.

The Challenge is focused on finding delivery systems that can be programmed with biological or chemical tags that correspond to specific target cells and tissues. These tags would direct the delivery systems and the genome editing therapies to the target cells or tissues—like mail being delivered to different zip codes. Such programmable delivery systems would improve gene editing efficacy by targeting diseases at their source and would enhance safety by reducing undesired impacts on other tissues or cells. Ultimately, the development of safe and effective programmable delivery technologies for genome editors that are applicable to multiple diseases would help advance the application of gene editing therapies into the clinic.

The Challenge also is interested in gene editing delivery technologies that can cross the blood-brain barrier (BBB). The BBB protects the brain by blocking harmful substances from entering the fluid of the central nervous system. Unfortunately, it also blocks the uptake of many therapeutics, hindering treatments for brain diseases. While viruses are one of the few approaches that can be used as delivery systems to cross the BBB, they are expensive and difficult to make. Therefore, there is a pressing need for effective non-viral technologies to deliver genome editing machinery across the BBB to a substantial proportion of clinically relevant brain cell types. Such technologies could have broad implications for the treatment of many neurogenetic diseases.

Solutions to both target areas would not only provide proof-of-concept for the delivery of genome editing therapeutics, but they could be adapted to deliver other types of therapies to treat common and rare diseases in general.

The first phase of the Challenge began on May 15, 2023 and will run until October 5, 2023. More information about the Challenge is available on the TARGETED Genome Editor Delivery Challenge website.


National Institutes of Health launch TARGETED Challenge,” NIH Common Fund, May 15, 2023

TARGETED Genome Editor Delivery Challenge (NIH Common Fund)

Somatic Cell Genome Editing Program (NIH Common Fund)

NIH Support: The SCGE program is led by the NIH Common Fund, the National Center for Advancing Translational Sciences (NCATS), and the National Institute of Neurological Disorders and Stroke (NINDS). The Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative and the National Heart, Lung, and Blood Institute (NHLBI) are also contributors to this Challenge.

Research!America’s National Health Research Forum

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Lawrence Tabak talks with Mary Woolley on stage at the 2023 National Health Research Forum at George Washington University
On Sept. 20, 2023, I attended Research!America’s National Health Research Forum held at George Washington University in Washington, D.C. Here I am pictured with Mary Woolley (right), President and CEO of Research!America. We had a great discussion on a number of topics, including NIH’s RECOVER initiative to address long COVID, plans to update the NIH mission statement, how to communicate science and how we can prepare the next generation of researchers for the challenges ahead.

Rice-Sized Device Tests Brain Tumor’s Drug Responses During Surgery

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Determining most effective tumor-specific drug. A transparent head with a brain tumor. A zoomed in version show a small cylinder with 10 tiny holes embedded in the tumor. Each hole has a different drug leaking out.
A device implanted into a tumor during surgery delivers tiny doses of up to 20 drugs to determine each treatment’s effects. Credit: Donny Bliss, NIH

Scientists have made remarkable progress in understanding the underlying changes that make cancer grow and have applied this knowledge to develop and guide targeted treatment approaches to vastly improve outcomes for people with many cancer types. And yet treatment progress for people with brain tumors known as gliomas—including the most aggressive glioblastomas—has remained slow. One reason is that doctors lack tests that reliably predict which among many therapeutic options will work best for a given tumor.

Now an NIH-funded team has developed a miniature device with the potential to change this for the approximately 25,000 people diagnosed with brain cancers in the U.S. each year [1]. When implanted into cancerous brain tissue during surgery, the rice-sized drug-releasing device can simultaneously conduct experiments to measure a tumor’s response to more than a dozen drugs or drug combinations. What’s more, a small clinical trial reported in Science Translational Medicine offers the first evidence in people with gliomas that these devices can safely offer unprecedented insight into tumor-specific drug responses [2].

These latest findings come from a Brigham and Women’s Hospital, Boston, team led by Pierpaolo Peruzzi and Oliver Jonas. They recognized that drug-screening studies conducted in cells or tissue samples in the lab too often failed to match what happens in people with gliomas undergoing cancer treatment. Wide variation within individual brain tumors also makes it hard to predict a tumor’s likely response to various treatment options.  

It led them to an intriguing idea: Why not test various therapeutic options in each patient’s tumor? To do it, they developed a device, about six millimeters long, that can be inserted into a brain tumor during surgery to deliver tiny doses of up to 20 drugs. Doctors can then remove and examine the drug-exposed cancerous tissue in the laboratory to determine each treatment’s effects. The data can then be used to guide subsequent treatment decisions, according to the researchers.

In the current study, the researchers tested their device on six study volunteers undergoing brain surgery to remove a glioma tumor. For each volunteer, the device was implanted into the tumor and remained in place for about two to three hours while surgeons worked to remove most of the tumor. Next, the device was taken out along with the last piece of a tumor at the end of the surgery for further study of drug responses.

Importantly, none of the study participants experienced any adverse effects from the device. Using the devices, the researchers collected valuable data, including how a tumor’s response changed with varying drug concentrations or how each treatment led to molecular changes in the cancerous cells.

More research is needed to better understand how use of such a device might change treatment and patient outcomes in the longer term. The researchers note that it would take more than a couple of hours to determine how treatments produce less immediate changes, such as immune responses. As such, they’re now conducting a follow-up trial to test a possible two-stage procedure, in which their device is inserted first using minimally invasive surgery 72 hours prior to a planned surgery, allowing longer exposure of tumor tissue to drugs prior to a tumor’s surgical removal.

Many questions remain as they continue to optimize this approach. However, it’s clear that such a device gives new meaning to personalized cancer treatment, with great potential to improve outcomes for people living with hard-to-treat gliomas.


[1] National Cancer Institute Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Brain and Other Nervous System Cancer.

[2] Peruzzi P et al. Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas. Science Translational Medicine DOI: 10.1126/scitranslmed.adi0069 (2023).


Brain Tumors – Patient Version (National Cancer Institute/NIH)

Pierpaolo Peruzzi (Brigham and Women’s Hospital, Boston, MA)

Jonas Lab (Brigham and Women’s Hospital, Boston, MA)

NIH Support: National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, National Institute of Neurological Disorders and Stroke

New Approach to ‘Liquid Biopsy’ Relies on Repetitive RNA in the Bloodstream

Posted on by Lawrence Tabak, D.D.S., Ph.D.

A nurse draws blood from the arm of a patient. To the side, RNA floats inside a vial of blood. The vial is labeled RNA from cancer cells.
Researchers have identified segments of noncoding RNA circulating in the blood that are early signs of cancer. Credit: Modified from Adobe Stock/ Andrey Popov; Donny Bliss, NIH

It’s always best to diagnose cancer at an early stage when treatment is most likely to succeed. Unfortunately, far too many cancers are still detected only after cancer cells have escaped from a primary tumor and spread to distant parts of the body. This explains why there’s been so much effort in recent years to develop liquid biopsies, which are tests that can pick up on circulating cancer cells or molecular signs of cancer in blood or other bodily fluids and reliably trace them back to the organ in which a potentially life-threatening tumor is growing.

Earlier methods to develop liquid biopsies for detecting cancers often have relied on the presence of cancer-related proteins and/or DNA in the bloodstream. Now, an NIH-supported research team has encouraging evidence to suggest that this general approach to detecting cancers—including aggressive pancreatic cancers—may work even better by taking advantage of signals from a lesser-known form of genetic material called noncoding RNA.

The findings reported in Nature Biomedical Engineering suggest that the new liquid biopsy approach may aid in the diagnosis of many forms of cancer [1]. The studies show that the sensitivity of the tests varies—a highly sensitive test is one that rarely misses cases of disease. However, they already have evidence that millions of circulating RNA molecules may hold promise for detecting cancers of the liver, esophagus, colon, stomach, and lung.

How does it work? The human genome contains about 3 billion paired DNA letters. Most of those letters are transcribed, or copied, into single-stranded RNA molecules. While RNA is best known for encoding proteins that do the work of the cell, most RNA never gets translated into proteins at all. This noncoding RNA includes repetitive RNA that can be transcribed from millions of repeat elements—patterns of the same few DNA letters occurring multiple times in the genome.

Common approaches to studying RNA don’t analyze repetitive RNA, so its usefulness as a diagnostic tool has been unclear—until recently. Last year, the lab of Daniel Kim at the University of California, Santa Cruz reported [2] that a key genetic mutation that occurs early on in some cancers causes repetitive RNA molecules to be secreted in large quantities from cancer cells, even at the earliest stages of cancer. Non-cancerous cells, by comparison, release much less repetitive RNA.

The findings suggested that liquid biopsy tests that look for this repetitive, noncoding RNA might offer a powerful new way to detect cancers sooner, according to the authors. But first they needed a method capable of measuring it. Due to its oftentimes uncertain functions, the researchers have referred to repetitive, noncoding RNA as “dark matter.”

Using a liquid biopsy platform they developed called COMPLETE-seq, Kim’s team trained computers to detect cancers by looking for patterns in RNA data. The platform enables sequencing and analysis of all protein coding and noncoding RNAs—including any RNA from more than 5 million repeat elements—present in a blood sample. They found that their classifiers worked better when repetitive RNAs were included. The findings lend support to the idea that repetitive, noncoding RNA in the bloodstream is a rich source of information for detecting cancers, which has previously been overlooked.

In a study comparing blood samples from healthy people to those with pancreatic cancer, the COMPLETE-seq technology showed that nearly all people in the study with pancreatic cancer had more repetitive, noncoding RNA in their blood samples compared to healthy people, according to the researchers. They used the COMPLETE-seq test on blood samples from people with other types of cancer as well. For example, their test accurately detected 91% of colorectal cancer samples and 93% of lung cancer samples.

They now plan to look at many more cancer types with samples from additional patients representing a broad range of cancer stages. The goal is to develop a single RNA liquid biopsy test that could detect multiple forms of cancer with a high degree of accuracy and specificity. They note that such a test might also be used to guide treatment decisions and more readily detect a cancer’s recurrence. The hope is that one day a comprehensive liquid biopsy test including coding and noncoding RNA will catch many more cancers sooner, when treatment can be most successful.


[1] RE Reggiardo et al. Profiling of repetitive RNA sequences in the blood plasma of patients with cancer. Nature Biomedical Engineering DOI: 10.1038/s41551-023-01081-7 (2023).

[2] RE Reggiardo et al. Mutant KRAS regulates transposable element RNA and innate immunity via KRAB zinc-finger genes. Cell Reports DOI: 10.1016/j.celrep.2022.111104 (2022).


Daniel Kim Lab (UC Santa Cruz)

Cancer Screening Overview (National Cancer Institute/NIH)

Early Detection (National Cancer Institute/NIH)

NIH Support: National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases

Mapping Immune Cell “Neighborhoods” in Psoriasis to Understand its Course

Posted on by Lawrence Tabak, D.D.S., Ph.D.

A light microscopy view of skin tissue shown as a map. A box of push pins are labeled Immune Cells. Pins are attached to areas in the dermis.
Researchers mapped immune cell “neighborhoods” in the skin of people with psoriasis compared to the healthy skin of people without psoriasis to learn more about the disease course and why it comes with more risk for other health problems. Credit: Donny Bliss, NIH

“Location, location, location.” While most of us know this phrase as a real estate adage, location—specifically that of various cell types—is becoming a key area of investigation in studying human disease. New techniques are enabling scientists to understand where certain cells are with respect to one another and how changes in their activity may affect your overall health.

In one recent example of the power of this approach, NIH-funded researchers [1] used a sophisticated method to map immune cells within human skin to get a more detailed picture of psoriasis, a common, chronic disease in which the immune system becomes overactive leading to skin inflammation. People with psoriasis develop patches of itchy, red, and flaky lesions on their skin, which can be mild to severe. For reasons that aren’t entirely clear, they’re also at higher risk for developing a wide range of other health conditions, including a unique form of arthritis known as psoriatic arthritis, diabetes, mental health issues, heart problems, and more.

The hope is that these newly drawn, precise maps of cellular “neighborhoods” in human skin will help chart the precise course of this disease to understand better the differences between mild and more severe forms. They may also yield important clues as to why people with psoriasis develop other health problems more often than people without psoriasis.

In the new study, a team including Jose Scher and Shruti Naik, NYU Langone, New York, analyzed immune cells within 25 skin samples from 14 volunteers, including those with active psoriasis, those with psoriasis but no active lesions, and people with healthy skin who do not have psoriasis. The researchers relied on a sophisticated approach called spatial transcriptomics [2] to map out what happens at the single-cell level within the samples.

In earlier approaches to single-cell analysis, researchers first would separate cells from the tissue they came from. While they could measure gene activity within those cells at the individual level, they couldn’t put things back together to see how they all fit. With spatial transcriptomics, it’s now possible to molecularly profile single cells to measure their activity in a tissue sample while also mapping their locations with respect to other cells.

The new study led to some intriguing findings. For instance, certain immune cells, specifically B cells, moved to the upper layers of the skin during active disease. That’s notable because prior studies had been unable to capture B cells in the skin adequately, and these cells are thought to play an important role in the disease.

Interestingly, the spatial cellular maps revealed inflammatory regions in both actively inflamed skin and in skin that appeared healthy. This finding highlights the fact that the inflammation that goes with psoriasis can affect the skin, and likely other parts of the body, in ways that aren’t easily observed. In future studies, the researchers want to explore how the presence of psoriasis and its underlying changes in immune cell activity may influence other organs and tissues beneath the skin.

Their fine-scale maps also showed increased gene activity in dozens of molecular pathways that are tied to metabolism and the control of lipid levels. That’s especially interesting because these factors are known to go awry in diabetes and heart conditions, which happen more often in people with psoriasis compared to those without. They also could see in their maps that this altered activity sometimes occurred in clear skin distant from any apparent lesions.

Having discovered such signals with potential consequences for other parts of the body, the researchers report that they’re working to understand how inflammatory immune cells and processes in the skin may lead to more widespread disease processes that affect other parts of the body. They plan to conduct similar studies in larger groups of people with and without active psoriasis lesions and studies following individuals with psoriasis over time. They’ll also explore questions about why people respond differently to the same anti-inflammatory treatment regimens.

To speed the process of discovery, they’ve made their maps and associated data freely available as a resource for the scientific community. About 7.5 million adults in the U.S. and millions more worldwide have psoriasis and associated psoriatic conditions [3]. The hope is that these maps will one day help to steer them toward a healthier future.


[1] Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems. Castillo RL, Sidhu I, Dolgalev I, Chu T, Prystupa A, Subudhi I, Yan D, Konieczny P, Hsieh B, Haberman RH, Selvaraj S, Shiomi T, Medina R, Girija PV, Heguy A, Loomis CA, Chiriboga L, Ritchlin C, Garcia-Hernandez ML, Carucci J, Meehan SA, Neimann AL, Gudjonsson JE, Scher JU, Naik S. Sci Immunol. 2023 Jun 8;8(84):eabq7991. doi: 10.1126/sciimmunol.abq7991.

[2] Method of the Year: spatially resolved transcriptomics. Marx V. Nat Methods. 2021 Jan;18(1):9-14. doi: 10.1038/s41592-020-01033-y.

[3] Psoriasis Prevalence in Adults in the United States. Armstrong AW, Mehta MD, Schupp CW, Gondo GC, Bell SJ, Griffiths CEM. JAMA Dermatol. 2021 Aug 1;157(8):940-946. doi: 10.1001/jamadermatol.2021.2007.


Psoriasis (National Institute of Arthritis and Musculoskeletal and Skin Diseases/NIH)

Jose Scher (NYU Langone Health, New York, NY)

Shruti Naik (NYU Langone Health, New York, NY)

NIH Support: National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases

Encouraging First-in-Human Results for a Promising HIV Vaccine

Posted on by Lawrence Tabak, D.D.S., Ph.D.

eOD-GT8 60-mer is injected into a cartoon woman's shoulder. Her body makes B-cells. Dashed arrows suggest that plasma cells will be created that make many antibodies. Also T-cells will be made by her body in response.
Researchers used a customized nanoparticle (top left) to learn more about guiding the immune system to mount a desired robust response, the type needed for an effective HIV vaccine. Credit: Donny Bliss, NIH

In recent years, we’ve witnessed some truly inspiring progress in vaccine development. That includes the mRNA vaccines that were so critical during the COVID-19 pandemic, the first approved vaccine for respiratory syncytial virus (RSV), and a “universal flu vaccine” candidate that could one day help to thwart future outbreaks of more novel influenza viruses.

Inspiring progress also continues to be made toward a safe and effective vaccine for HIV, which still infects about 1.5 million people around the world each year [1]. A prime example is the recent first-in-human trial of an HIV vaccine made in the lab from a unique protein nanoparticle, a molecular construct measuring just a few billionths of a meter.

The results of this early phase clinical study, published recently in the journal Science Translational Medicine [2] and earlier in Science [3], showed that the experimental HIV nanoparticle vaccine is safe in people. While this vaccine alone will not offer HIV protection and is intended to be part of an eventual broader, multistep vaccination regimen, the researchers also determined that it elicited a robust immune response in nearly all 36 healthy adult volunteers.

How robust? The results show that the nanoparticle vaccine, known by the lab name eOD-GT8 60-mer, successfully expanded production of a rare type of antibody-producing immune B cell in nearly all recipients.

What makes this rare type of B cell so critical is that it is the cellular precursor of other B cells capable of producing broadly neutralizing antibodies (bnAbs) to protect against diverse HIV variants. Also very good news, the vaccine elicited broad responses from helper T cells. They play a critical supportive role for those essential B cells and their development of the needed broadly neutralizing antibodies.

For decades, researchers have brought a wealth of ideas to bear on developing a safe and effective HIV vaccine. However, crossing the finish line—an FDA-approved vaccine—has proved profoundly difficult.

A major reason is the human immune system is ill equipped to recognize HIV and produce the needed infection-fighting antibodies. And yet the medical literature includes reports of people with HIV who have produced the needed antibodies, showing that our immune system can do it.

But these people remain relatively rare, and the needed robust immunity clocks in only after many years of infection. On top of that, HIV has a habit of mutating rapidly to produce a wide range of identity-altering variants. For a vaccine to work, it most likely will need to induce the production of bnAbs that recognize and defend against not one, but the many different faces of HIV.

To make the uncommon more common became the quest of a research team that includes scientists William Schief, Scripps Research and IAVI Neutralizing Antibody Center, La Jolla, CA; M. Juliana McElrath, Fred Hutchinson Cancer Center, Seattle; and Kristen Cohen, a former member of the McElrath lab now at Moderna, Cambridge, MA. The team, with NIH collaborators and support, has been plotting out a stepwise approach to train the immune system into making the needed bnAbs that recognize many HIV variants.

The critical first step is to prime the immune system to make more of those coveted bnAb-precursor B cells. That’s where the protein nanoparticle known as eOD-GT8 60-mer enters the picture.

This nanoparticle, administered by injection, is designed to mimic a small, highly conserved segment of an HIV protein that allows the virus to bind and infect human cells. In the body, those nanoparticles launch an immune response and then quickly vanish. But because this important protein target for HIV vaccines is so tiny, its signal needed amplification for immune system detection.

To boost the signal, the researchers started with a bacterial protein called lumazine synthase (LumSyn). It forms the scaffold, or structural support, of the self-assembling nanoparticle. Then, they added to the LumSyn scaffold 60 copies of the key HIV protein. This louder HIV signal is tailored to draw out and engage those very specific B cells with the potential to produce bnAbs.

As the first-in-human study showed, the nanoparticle vaccine was safe when administered twice to each participant eight weeks apart. People reported only mild to moderate side effects that went away in a day or two. The vaccine also boosted production of the desired B cells in all but one vaccine recipient (35 of 36). The idea is that this increase in essential B cells sets the stage for the needed additional steps—booster shots that can further coax these cells along toward making HIV protective bnAbs.

The latest finding in Science Translational Medicine looked deeper into the response of helper T cells in the same trial volunteers. Again, the results appear very encouraging. The researchers observed CD4 T cells specific to the HIV protein and to the LumSyn in 84 percent and 93 percent of vaccine recipients. Their analyses also identified key hotspots that the T cells recognized, which is important information for refining future vaccines to elicit helper T cells.

The team reports that they’re now collaborating with Moderna, the developer of one of the two successful mRNA-based COVID-19 vaccines, on an mRNA version of eOD-GT8 60-mer. That’s exciting because mRNA vaccines are much faster and easier to produce and modify, which should now help to move this line of research along at a faster clip.

Indeed, two International AIDS Vaccine Initiative (IAVI)-sponsored clinical trials of the mRNA version are already underway, one in the U.S. and the other in Rwanda and South Africa [4]. It looks like this team and others are now on a promising track toward following the basic science and developing a multistep HIV vaccination regimen that guides the immune response and its stepwise phases in the right directions.

As we look back on more than 40 years of HIV research, it’s heartening to witness the progress that continues toward ending the HIV epidemic. This includes the recent FDA approval of the drug Apretude, the first injectable treatment option for pre-exposure prevention of HIV, and the continued global commitment to produce a safe and effective vaccine.


[1] Global HIV & AIDS statistics fact sheet. UNAIDS.

[2] A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses. Cohen KW, De Rosa SC, Fulp WJ, deCamp AC, Fiore-Gartland A, Laufer DS, Koup RA, McDermott AB, Schief WR, McElrath MJ. Sci Transl Med. 2023 May 24;15(697):eadf3309.

[3] Vaccination induces HIV broadly neutralizing antibody precursors in humans. Leggat DJ, Cohen KW, Willis JR, Fulp WJ, deCamp AC, Koup RA, Laufer DS, McElrath MJ, McDermott AB, Schief WR. Science. 2022 Dec 2;378(6623):eadd6502.

[4] IAVI and Moderna launch first-in-Africa clinical trial of mRNA HIV vaccine development program. IAVI. May 18, 2022.


Progress Toward an Eventual HIV Vaccine, NIH Research Matters, Dec. 13, 2022.

NIH Statement on HIV Vaccine Awareness Day 2023, Auchincloss H, Kapogiannis, B. May, 18, 2023.

HIV Vaccine Development (National Institute of Allergy and Infectious Diseases/NIH)

International AIDS Vaccine Initiative (IAVI) (New York, NY)

William Schief (Scripps Research, La Jolla, CA)

Julie McElrath (Fred Hutchinson Cancer Center, Seattle, WA)

McElrath Lab (Fred Hutchinson Cancer Center, Seattle, WA)

NIH Support: National Institute of Allergy and Infectious Diseases

DNA Barcodes Make for Better Single-Cell Analysis

Posted on by Dr. Francis Collins

Variations within neurons

Caption: Single-cell analysis helps to reveal subtle, but important, differences among human cells, including many types of brain cells.
Credit: Shutterstock, modified by Ryan M. Mulqueen

Imagine how long it would take to analyze the 37 trillion or so cells that make up the human body if you had to do it by hand, one by one! Still, single-cell analysis is crucial to gaining a comprehensive understanding of our biology. The cell is the unit of life for all organisms, and all cells are certainly not the same. Think about it: even though each cell contains the same DNA, some make up your skin while others build your bones; some of your cells might be super healthy while others could be headed down the road to cancer or Alzheimer’s disease.

So, it’s no surprise that many NIH-funded researchers are hard at work in the rapidly emerging field known as single-cell analysis. In fact, one team recently reported impressive progress in improving the speed and efficiency of a method to analyze certain epigenetic features of individual cells [1]. Epigenetics refers to a multitude of chemical and protein “marks” on a cell’s DNA—patterns that vary among cells and help to determine which genes are switched on or off. That plays a major role in defining cellular identity as a skin cell, liver cell, or pancreatic cancer cell.

The team’s rather simple but ingenious approach relies on attaching a unique combination of two DNA barcodes to each cell prior to analyzing epigenetic marks all across the genome, making it possible for researchers to pool hundreds of cells without losing track of each of them individually. Using this approach, the researchers could profile thousands of individual cells simultaneously for less than 50 cents per cell, a 50- to 100-fold drop in price. The new approach promises to yield important insights into the role of epigenetic factors in our health, from the way neurons in our brains function to whether or not a cancer responds to treatment.

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