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Lawrence Tabak, D.D.S., Ph.D.

The Chemistry Clicked: Two NIH-Supported Researchers Win 2022 Nobel Prize in Chemistry

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Illustrations of Carolyn R. Bertozzi and K. Barry Sharpless drawn by Niklas Elmehed

Through the years, NIH has supported a total of 169 researchers who have received or shared 101 Nobel Prizes. That’s quite a testament to the world-leading science that NIH pursues and its continued impact on improving human health and well-being.

Those numbers include the news late last week that the 2022 Nobel Prize in Chemistry was shared by two long-time grantees for their work on a transformative scientific approach known as “click chemistry.” This form of chemistry has made it possible for researchers to snap together, like LEGO pieces, molecular building blocks to form hybrid biomolecules, often with easy-to-track imaging agents attached. Not only has click chemistry expanded our ability to explore the molecular underpinnings of a wide range of biological processes, but it has provided us with new tools for developing drugs, diagnostics, and a wide array of “smart” materials.

For K. Barry Sharpless, Scripps Research, La Jolla, CA, October 5, 2022 marked the second time that he’s received an early-morning congratulatory call from The Royal Swedish Academy of Sciences. The first such call came in 2001, when Sharpless got the news that he was a co-winner of the Nobel Prize in Chemistry for his discovery of asymmetric catalytic reactions.

This time around, Sharpless was recognized for his groundbreaking studies in the mid-1990s with click chemistry, a term that he coined himself. His initial work established click chemistry as a fast-and-reliable way to attach molecules of interest in the lab [1]. He and co-recipient Morten Meldal, University of Copenhagen, Denmark, who is not funded by NIH, then independently introduced a copper-catalyzed click that further refined the chemistry and helped popularize it across biology and the material sciences [2,3].

For Carolyn R. Bertozzi of Stanford University, Palo Alto, CA, it is her first Nobel. Bertozzi was recognized for expanding the use of click chemistry with so-called bioorthogonal chemistry, which is a copper-free version of the approach that can be used inside living cells without the risk of metal-associated toxicities [4,5].

Bertozzi’s work has been especially interesting to me because of her focus on glycans, which I’ve studied throughout my career. Glycans are the carbohydrate molecules that coat the surfaces of our cells and most secreted proteins. They are essential to life, and, in higher organisms, play fundamental roles in basic processes such as metabolism, immunity, and cellular communication.

Glycans also remain poorly understood, largely because, until recently, they have been so difficult for basic scientists to study with traditional techniques. That has changed with development of new tools to study glycans and the enzymes that assemble them. My long-time collaborator, Kelly Ten Hagen, a senior investigator at NIH’s National Institute of Dental and Craniofacial Research, and I collaborated with Carolyn on identifying small molecules that inhibit the enzyme responsible for the first step in mucin-type O-glycosylation [6]

In the early 2000s, Bertozzi and her team introduced bioorthogonal chemistry, which enabled researchers to label glycans and visualize them in a range of cells and living organisms. Her team’s pioneering approach quickly became an essential tool in basic science labs around the world that study glycans, leading to a number of stunning discoveries that would have otherwise been difficult or impossible.

For clinical researchers, click chemistry has emerged as a workhorse in drug discovery and the improved targeting of cancer chemotherapies and other small-molecule drugs. The approach also is being used to improve delivery of antibody-based therapies and to create new biomaterials. Meanwhile, in the material sciences, click chemistry has been used to solve a number of problems in working with polymers and to expand their industrial uses.

Click chemistry is an excellent example of how advances in basic science can build the foundation for a wide range of practical applications, including those aimed at improving human health. It also highlights the value of strong, sustained public funding for fundamental research, and NIH is proud to have supported Sharpless continuously since 1975 and Bertozzi since 1999. I send my sincere congratulations to both of these most-deserving scientists.


[1] Click Chemistry: Diverse chemical function from a few good reactions. Kolb, HC, Finn, MG, Sharpless, KB. Angew. Chem. Int. Ed. 2001, 40 (11), 2004–2021

[2] A stepwise huisgen cycloaddition process: Copper(I)-catalyzed regioselective “Llgation” of azides and terminal alkynes. Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002, 41 (14), 2596–2599.

[3] Peptidotriazoles on solid phase: [1,2,3]-Triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. Tornøe CW, Sengeløv H, Meldal M. J. Org. Chem. 2002, 67 (9), 3057–3064.

[4] A strain-promoted [3 + 2] azide−alkyne cycloaddition for covalent modification of biomolecules in living systems. Agard NJ, Prescher JA, Bertozzi CR. J. Am. Chem. Soc. 2004, 126 (46), 15046–15047

[5] In vivo imaging of membrane associated glycans in developing zebrafish. Laughlin ST, Baskin JM, Amacher SL, Bertozzi CR. Science 2008, 320 (5876), 664–667.

[6] Small molecule inhibitors of mucin-type O-glycosylation from a uridine-based library. Hang, HC, Yu, C, Ten Hagen, KG, Tian, E, Winans, KA, Tabak, LA, Bertozzi, Chem Biol. 2004 Jul;11(7):1009-1016.


The Nobel Prize in Chemistry 2022 (The Royal Swedish Academy of Sciences, Stockholm)

Video: Announcement of the 2022 Nobel Prize in Chemistry (YouTube)

Click Chemistry and Bioorthogonal Chemistry (The Royal Swedish Academy of Sciences)

Sharpless Lab (Scripps Research, La Jolla, CA)

Bertozzi Group (Stanford University, Palo Alto, CA)

NIH Support:

K. Barry Sharpless: National Institute of General Medical Sciences

Carolyn R. Bertozzi: National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences

Wearable Sensor Promises More Efficient Early Cancer Drug Development

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A labeled sensor rests on the surface of the skin. Under the sensor, beneath the skin in a tumor. A graph shows the tumor's size over time.

Wearable electronic sensors hold tremendous promise for improving human health and wellness. That promise already runs the gamut from real-time monitoring of blood pressure and abnormal heart rhythms to measuring alcohol consumption and even administering vaccines.

Now a new study published in the journal Science Advances [1] demonstrates the promise of wearables also extends to the laboratory. A team of engineers has developed a flexible, adhesive strip that, at first glance, looks like a Band-Aid. But this “bandage” actually contains an ultra-sensitive, battery-operated sensor that’s activated when placed on the skin of mouse models used to study possible new cancer drugs.

This sensor is so sensitive that it can detect, in real time, changes in the size of a tumor down to one-hundredth of a millimeter. That’s about the thickness of the plastic cling wrap you likely have in your kitchen! The device beams those measures to a smartphone app, capturing changes in tumor growth minute by minute over time.

The goal is to determine much sooner—and with greater automation and precision—which potential drug candidates undergoing early testing in the lab best inhibit tumor growth and, consequently, should be studied further. In their studies in mouse models of cancer, researchers found the new sensor could detect differences between tumors treated with an active drug and those treated with a placebo within five hours. Those quick results also were validated using more traditional methods to confirm their accuracy.

The device is the work of a team led by Alex Abramson, a former post-doc with Zhenan Bao, Stanford University’s School of Engineering, Palo Alto, CA. Abramson has since launched his own lab at the Georgia Institute of Technology, Atlanta.

The Stanford team began looking for a technological solution after realizing the early testing of potential cancer drugs typically requires researchers to make tricky measurements using pincer-like calipers by hand. Not only is the process tedious and slow, it’s less than an ideal way to capture changes in soft tissues with the desired precision. The imprecision can also lead to false leads that won’t pan out further along in the drug development pipeline, at great time and expense to their developers.

To refine the process, the NIH-supported team turned to wearable technology and recent advances in flexible electronic materials. They developed a device dubbed FAST (short for Flexible Autonomous Sensor measuring Tumors). Its sensor, embedded in a skin patch, is composed of a flexible and stretchable, skin-like polymer with embedded gold circuitry.

Here’s how FAST works: Coated on top of the polymer skin patch is a layer of gold. When stretched, it forms small cracks that change the material’s electrical conductivity. As the material stretches, even slightly, the number of cracks increases, causing the electronic resistance in the sensor to increase as well. As the material contracts, any cracks come back together, and conductivity improves.

By picking up on those changes in conductivity, the device measures precisely the strain on the polymer membrane—an indication of whether the tumor underneath is stable, growing, or shrinking—and transmits that data to a smartphone. Based on that information, potential therapies that are linked to rapid tumor shrinkage can be fast-tracked for further study while those that allow a tumor to continue growing can be cast aside.

The researchers are continuing to test their sensor in more cancer models and with more therapies to extend these initial findings. Already, they have identified at least three significant advantages of their device in early cancer drug testing:

• FAST is non-invasive and captures precise measurements on its own.
• It can provide continuous monitoring, for weeks, months, or over the course of study.
• The flexible sensor fully surrounds the tumor and can therefore detect 3D changes in shape that would be hard to pick up otherwise in real-time with existing technologies.

By now, you are probably asking yourself: Could FAST also be applied as a wearable for cancer patients to monitor in real-time whether an approved chemotherapy regimen is working? It is too early to say. So far, FAST has not been tested in people. But, as highlighted in this paper, FAST is off to, well, a fast start and points to the vast potential of wearables in human health, wellness, and also in the lab.


[1] A flexible electronic strain sensor for the real-time monitoring of tumor regression. Abramson A, Chan CT, Khan Y, Mermin-Bunnell A, Matsuhisa N, Fong R, Shad R, Hiesinger W, Mallick P, Gambhir SS, Bao Z. Sci Adv. 2022 Sep 16;8(37):eabn6550.


Stanford Wearable Electronics Initiative (Stanford University, Palo Alto, CA)

Bao Group (Stanford University)

Abramson Lab (Georgia Institute of Technology, Atlanta)

NIH Support: National Institute of Biomedical Imaging and Bioengineering

Time to Get Boosted

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Dr. Tabak receiving a vaccination in his shoulder
I got my COVID-19 bivalent vaccine booster last weekend. The Moderna and the Pfizer-BioNTech COVID-19 bivalent vaccine boosters should be now widely available in communities around the country. If it’s been two months since you completed your primary vaccination series or received a booster, you are eligible to receive the bivalent booster. I encourage all those eligible to get the updated vaccine booster, especially with winter on the way.

Dedicating Roy Blunt Center for Alzheimer’s Disease and Related Dementias

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Dr. Tabak speaks at a podium, four other people sit to his sides
On September 19, I welcomed everyone to the dedication of the brand-new Roy Blunt Center for Alzheimer’s Disease and Related Dementias, which is located on the main NIH campus, Bethesda, MD. Seated behind me (l-r) are former NIH director Francis Collins; Dawn Beraud, NIH’s National Institute on Aging; Senator Roy Blunt of Missouri; and Congressman Tom Cole of Oklahoma. The 24,000-square foot building, which includes 12,000 square feet of laboratory space, will house the NIH Intramural Research Program’s Center for Alzheimer’s and Related Dementias (CARD). The facility is named in honor of Senator Blunt, who will be retiring from Congress, to recognize his extraordinary leadership and unwavering commitment to speed medical progress in this important area that touches far too many lives and families. Credit: NIH

Celebrating NIH and Life-Saving Science During Rally for Medical Research

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Dr. Tabak at a podium with sign saying Rally for Medical Research, Capitol Hill Day
It was my pleasure to take part in a recent reception held on Capitol Hill to celebrate the lifesaving science that NIH supports. The well-attended evening reception was part of the Rally for Medical Research Capitol Hill Day, an annual event that is organized by the American Association for Cancer Research and supported by nearly 350 partnering organizations I spoke for several minutes about NIH’s role in furthering medical research and innovation, and how this wise national investment has led to more progress, more hope, and more lives saved. The reception was held in the Rayburn House Office Building on September 13. Credit:

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