Category Archives: Biochemistry

Biochemistry

Science is Looking at Ways to Self-Heal Cellphones – AZoNano

Almost all cellphone users experience a cracked screen at some point. This frustrating issue can be disappointing and is expensive to fix.

Two scientists from Concordias OH Research Group in the Faculty of Arts and Science are exploring ways to self-heal the cellphone, and their research could have wider implications.

One of the major difficulties in these types of projects is to maintain a balance between the mechanical and self-healing properties.

Twinkal Patel (BSc 17), PhD Candidate and Study First Author, Department of Chemistry and Biochemistry, Concordia University

The study titled Self-Healable Reprocessable Triboelectric Nanogenerators Fabricated with Vitrimeric Poly(hindered Urea) Networks has been reported in the ACS Nano journal.

Patel states this study excels from similar work on the topic due to its focal point on temperature.

Our goal is to not compromise the toughness of the network while adding dynamic ability to self-heal damage and scratches. We focus on achieving complete healing of scratches at just room temperature. This feature sets our research apart from others.

Twinkal Patel (BSc 17), PhD Candidate and Study First Author, Department of Chemistry and Biochemistry, Concordia University

The research group's self-healing polymer networks were made via highly simple synthetic routes. The materials developed showed outstanding results at room temperature.

These materials can quickly repair damages and cracks due to the self-healing mechanism. As a result, these materials save consumers time and money while also extending the lifespan of the material used and reducing environmental burden, stated Pothana Gandhi Nellepalli, Horizon postdoctoral fellow and co-author on the paper.

Patel credits the success of the project to the Oh Research Group, headed by John Oh, professor and Canada Research Chair (Tier II) in Nanobioscience in the Department of Chemistry and Biochemistry.

Oh stated, Working here has been a great experience. During my time here I have met amazing and supportive members who have made this lab feel like a second family. I am very thankful for the mentorship I received from my supervisor to publish my first paper. I feel accomplished to see the hard work Ive done be published.

In the future, I would like to use self-healing polymer networks for improving the battery life of triboelectric nanogenerators. This same technology could definitely be used to extend the lifespan of cellphone batteries. In the future, we would be able to charge them just by walking.

Twinkal Patel (BSc 17), PhD Candidate and Study First Author, Department of Chemistry and Biochemistry, Concordia University

This technology enables a device to store energy and convert it into electricity by applying repeated movement. One can think of LED lights that are activated when they pass by.

Patel, T., et al. (2021) Self-Healable Reprocessable Triboelectric Nanogenerators Fabricated with Vitrimeric Poly (hindered Urea) Networks. ACS Nano. doi.org/10.1021/acsnano.0c03819.

Source: https://www.concordia.ca/

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Science is Looking at Ways to Self-Heal Cellphones - AZoNano

Biochemistry

Merck Foundation to fund professorships for early-career physician-scientists Washington University School of Medicine in St. Louis – Washington…

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Gift aimed at supporting School of Medicine researchers from populations underrepresented in medicine, biomedical sciences

The Merck Foundation has made a $2 million commitment to Washington University School of Medicine in St. Louis to establish two endowed assistant professorships each a Roger M. Perlmutter Career Development Professorship to support early-career physician-scientists from populations that are historically underrepresented in medicine and biomedical sciences. The professorships are named for Roger M. Perlmutter, MD, PhD, (pictured), a graduate of Washington Universitys Medical Scientist Training Program and, later, head of research and development at Merck. Monica Chang-Panesso, MD, an assistant professor of medicine, will receive the first such professorship.

The Merck Foundation has made a $2 million commitment to Washington University School of Medicine in St. Louis to establish two endowed assistant professorships supporting early-career physician-scientists from populations that are historically underrepresented in medicine and biomedical sciences.

Named for Roger M. Perlmutter, MD, PhD, a graduate of Washington Universitys Medical Scientist Training Program who later went on to lead research and development at Merck, the professorships will help advance the work of assistant professors pursuing promising medical research.

Chang-Panesso

The first Roger M. Perlmutter Career Development Professorship will be awarded to Monica Chang-Panesso, MD, an assistant professor of medicine in the Division of Nephrology. Another School of Medicine faculty member will be chosen for a second Perlmutter professorship in the near future.

The experience that I had at Washington University School of Medicine was transformational; the six years that I spent there made all the difference in terms of my ability to pursue a career in science and in drug discovery, Perlmutter said. Time and again, Washington University School of Medicine, in its teaching mission, its research mission and its mission of clinical translation, has done more than other academic medical centers to advance the cause of medical practice. I am deeply honored to have this gift from the Merck Foundation, which bears my name, to help further the cause of this great academic medical center.

The new career development professorships will provide support for faculty from populations underrepresented in medicine as they build their research programs. Once a recipient achieves tenure and transitions to the next career level, the professorship will be awarded to another faculty member.

Helping to create opportunities for physician-scientists to focus on research and develop as investigators is deeply important to the School of Medicine and is one of the core values that has distinguished WashU for many decades, said David H. Perlmutter, MD, the George and Carol Bauer Dean of the School of Medicine, executive vice chancellor for medical affairs, and the Spencer T. and Ann W. Olin Distinguished Professor. By providing support in the critical early phases of the career,these professorships, which are also enhanced by the prestige of Dr. Roger M. Perlmutters many career accomplishments as a physician-scientist, will better position us to addressthe urgent need for more physician-scientists from populations that historically have been excluded from medicine.

Li

Dean Y. Li, MD, PhD, Merck executive vice president and president of Merck Research Laboratories, and successor to Roger M. Perlmutter at Merck, explained that the Merck Foundation decided to honor Roger M. Perlmutters career by making a gift in his name to an institution with which he holds a long and proud association. Providing support to boost the careers of young physician-scientists seemed more than fitting.

The physician-scientist is critical for an academic medical center such as WashU, said Li, also a graduate of the universitys Medical Scientist Training Program. You have the science, and you have your clinical mission. The person who ties that together is the physician-scientist. Focusing on young scientists, especially physician-scientists at the early stages, is where the need is.

Chang-Panesso, the first faculty member named to a Perlmutter professorship, studies molecular mechanisms that impair the regenerative response after acute kidney injury, particularly when, in older people, the kidneys suddenly stop working as they should. Her current research, supported by a five-year grant from the National Institutes of Health (NIH), seeks new therapeutic targets and clinical interventions to improve the success of kidney repair in older patients.

I am very honored to be the recipient of the Roger M. Perlmutter Career Development Professorship, Chang-Panesso said.It is an amazing initiative supporting the career development of underrepresented physician-scientists, and I am very grateful to have been chosen.

Born and raised in Colombia, Chang-Panesso completed her undergraduate and postgraduate training in the United States, including a bachelors degree in biochemistry from the University of Texas at Arlington and a medical degree from the Texas Tech University Health Sciences Center School of Medicine in Lubbock, Texas.

She completed her residency at the University of Texas Southwestern Medical Center at Dallas and a nephrology fellowship at the Brigham and Womens Hospital/Massachusetts General Hospital program in Boston. She joined Washington University as a postdoctoral research scholar in 2015 and was promoted to assistant professor of medicine in 2018.

As a bilingual physician with Hispanic and Chinese roots, she is well aware that the rate of kidney disease is higher among racial and ethnic minorities. She hopes her career as a physician-scientist will help her identify treatments that will make a beneficial impact in these communities.

Roger M. Perlmutter earned his medical and doctoral degrees from Washington University in 1979. A member of the School of Medicine National Council since 2005, he received the universitys Distinguished Alumni Award in 2018.

Perlmutters family includes two more Washington University graduates. His wife, Joan Kreiss, an infectious diseases specialist, earned a medical degree in 1978. His son, Noah, earned an undergraduate degree from Arts & Sciences in 2020.

Before assuming leadership roles in industry, Perlmutter was a professor in the departments of immunology, biochemistry and medicine at the University of Washington, Seattle. He also served as a Howard Hughes Medical Institute investigator and chaired the Department of Immunology there. He is a fellow of the American Academy of Arts and Sciences and the American Association for the Advancement of Science, and past president of the American Association of Immunologists.

Perlmutter joined Merck Research Laboratories in 1997 as executive vice president of basic and preclinical research. From 2001 to 2012, he served as executive vice president and head of research and development at Amgen. He returned to Merck in 2013, serving as executive vice president and president of Merck Research Laboratories until his retirement in 2020. He became chief executive officer of Eikon Therapeutics, a company that employs super-resolution microscopy to pursue the discovery of new medicines, in 2021.

During his academic and corporate careers, Perlmutter has supervised the discovery, development and subsequent approval of novel medicines addressing major inflammatory and endocrinologic diseases, as well as a breakthrough oncology therapy that works with the immune system to help fight certain types of cancer.

Under his leadership, Merck received more than 100 regulatory approvals for its medicines and vaccines globally, including more than 15 novel vaccines and therapeutics for multiple cancers, diabetes and infections caused by Ebola virus, human immunodeficiency virus, hepatitis C virus and cytomegalovirus.

Washington University School of Medicines 1,700 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, consistently ranking among the top medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Merck Foundation to fund professorships for early-career physician-scientists Washington University School of Medicine in St. Louis - Washington...

Biochemistry

Job Dekker and Katherine Fitzgerald elected to National Academy of Medicine – UMass Medical School

UMass Chan Medical School scientists Job Dekker, PhD, and Katherine A. Fitzgerald, PhD, have been elected to the National Academy of Medicine for their distinguished contributions to medicine and health.

According to National Academy of Medicine President Victor J. Dzau, MD, who received an honorary degree from the Medical School in 2015, this is the academys most diverse class of new members, comprising approximately 50 percent women and 50 percent racial and ethnic minorities. This class represents many identities and experiencesall of which are absolutely necessary to address the existential threats facing humanity. I look forward to working with all of our new members in the years ahead, said Dr. Dzau.

New members are elected by current members through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care and public health.

Dr. Dekker, Howard Hughes Medical Institute investigator, the Joseph J. Byrne Chair in Biomedical Research, professor of biochemistry & molecular pharmacology and systems biology, was recognized for introducing the groundbreaking concept that matrices of genomic interactions can be used to determine chromosome conformation.

The Dekker lab studies how a genome is organized in three dimensions inside the nucleus. Although DNA is composed of a linear sequence of bases, it doesnt exist inside the cell nucleus in a simple, straight line. More like a ball of cooked spaghetti, the genome folds and loops back on itself so it can fit inside the tight confines of the nucleus. The shape it takes has a profound influence on which genes in a cell are turned on or turned off, and as a consequence, on health and disease. Many diseases, including cancer, are characterized by alterations in the spatial organization of the genome. This 3D architecture varies from cell type to cell type and even between cell states.

To study this 3D structure, Dekker developed chromosome conformation capture technologies, biochemical techniques for determining how DNA segments interact and are linked to one another. This technology is the heart of the 3C, 5C, Hi-C and Micro-C tools used by researchers worldwide to map the structure and organization of chromosomes inside cells.

Dekker received his PhD from Utrecht University in 1997 and joined UMass Chan in 2003.

Dr. Fitzgerald, the Worcester Foundation for Biomedical Research Chair, professor of medicine, vice chair for research in the Department of Medicine and director of the Program in Innate Immunity, was named to the academy for her pioneering work on innate immune receptors, signaling pathways and regulation of inflammatory gene expression.

Research in the Fitzgerald lab is focused on understanding the molecular mechanisms controlling the inflammatory process. Fitzgerald and her team use immunology, biochemistry, molecular biology and genetics to determine how the immune system discriminates between pathogens and host molecules to both protect the host from infection and avoid damaging inflammatory diseases. Fitzgerald has made numerous novel discoveries, including the identification of Toll-like receptor adapter molecules; TANK binding kinase-1 (TBK1) as the IRF3 kinase; identification of the AIM2 inflammasome; defined key regulators of the NLRP3 inflammasome; and uncovered new evidence for the importance of long-coding RNAs in innate immunity.

Fitzgerald, who joined the faculty in 2004, has a bachelors degree in biochemistry from University College Cork, and a PhD from Trinity College Dublin. She was elected to the American Academy of Microbiology in 2020 and the National Academy of Sciences in 2021.

The National Academy of Medicine, formerly the Institute of Medicine, was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues.

The National Academy of Medicine works together with the National Academy of Sciences and National Academy of Engineering to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering and medicine.

Related stories on UMassMed News:UMass Chan Medical School establishes new Department of Systems BiologyUMMS scientists to expand 4D nucleome research with $13 million NIH grantsKatherine Fitzgerald and Nikolaus Grigorieff elected to National Academy of Sciences

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Job Dekker and Katherine Fitzgerald elected to National Academy of Medicine - UMass Medical School

Biochemistry

Radioactive metals for medicine get a boost from recently discovered protein | Penn State University – Penn State News

UNIVERSITY PARK, Pa. A protein can be used to recover and purify radioactive metals such as actinium that could be beneficial for next-generation drugs used in cancer therapies and medical imaging, according to new research from Penn State and Lawrence Livermore National Laboratory (LLNL).

Radioactive metals are used in a variety of medical imaging and therapeutic applications. Actinium is a promising candidate for next-generation cancer therapies, and actinium-based therapies have treatment efficacy hundreds of times higher than current drugs. However, the chemistry of this metal is not well understood, and there are several limitations in the supply chain that have kept actinium-based drugs from reaching the market.

In this study, our team took advantage of a protein my lab previously discovered called lanmodulin and showed that it can be used to improve and simplify the recovery and purification of actinium, said Joseph Cotruvo Jr., assistant professor of chemistry at Penn State and an author of the paper. The research team presents their results in a paper appearing Oct. 20 in the journal Science Advances.

A protein can be used to recover and purify radioactive metals such as actinium, pictured here, that could be beneficial for next-generation drugs used in cancer therapies and medical imaging.

IMAGE: Oak Ridge National Laboratory/Wikimedia Commons

Radioactive metals used in medical applications must be purified to extremely high levels through lengthy processes and, to minimize toxicity in the patient, they must form complexes with molecules called chelators that are tailored to bind the radioactive metal ions. The vast majority of these chelators are synthetic molecules that are arrived at through trial and error. In addition to these challenges, the actinium supply chain faces several difficulties. Actinium is extremely rare and must be produced in nuclear reactors or other large instruments, and knowledge of the elements chemistry, which is necessary to develop optimal chelators, is limited.

These challenges exist even for medical isotopes in relatively widespread use, such as radioactive yttrium, but they are even more taxing in the case of actinium, said Gauthier Deblonde, a scientist at LLNL and lead author of the paper.

Because actinium is so rare, research efforts to understand and harness actinium chemistry have thus far focused on reusing or adapting similar known synthetic molecules used in the nuclear chemistry field, but results have been limited. The new research took a drastically different approach, leveraging the natural protein lanmodulin, which is exceptionally good at binding to valuable metals called rare Earth elements. This new strategy not only improves and simplifies the purification processes for actinium but can also be used to recover and detect other radioactive elements, even at extremely low levels.

The team showed how lanmodulin can be used to bind to, recover, and purify actinium (at least 99.5% purity obtained in a single step), as well as another medically relevant radioisotope, yttrium-90, which is used in cancer therapies and diagnostics. The unprecedented efficiency and simplicity of the protein-based approach also allows preparation of actinium at much lower cost and makes probing its chemistry more convenient. The process is likely extendable to many other radioactive isotopes used in radiation therapy and imaging.

Our new technique represents a paradigm shift not just in the development of actinium chemistry and actinium-based pharmaceuticals, but also in nuclear medicine more generally, said Cotruvo.

This study marks the first time actinium has been characterized bound to a protein important knowledge if it may eventually be used inside humans. The researchers found that lanmodulin is so efficient compared to classic molecules that it specifically binds to actinium even in the presence of large quantities of impurities, like radium and strontium, or elements that are common in the body like calcium, zinc and copper. The study also demonstrates that the protein is more effective at binding actinium than binding rare earth elements, the metals it binds to in nature.

Lanmodulins tight and specific binding allowed us to easily access minute quantities of radioactive metals, where traditional technologies based on synthetic chelators fail, Deblonde said. What we accomplished here was simply unfathomable a few years ago. The unique combination of skills in radiochemistry, metal separation, and biochemistry at LLNL and Penn State made this possible.

The research not only offers insights into the fundamental chemistry of actinium but also suggests that the actinium-lanmodulin complex could be the basis for new actinium pharmaceuticals, as lanmodulin in some ways outperforms the synthetic chelators currently used with radioactive metals in the clinic and clinical trials.

We believe that our results unify the fields of metal separations and biochemistry and have strong potential to revolutionize several critical steps in medicinal chemistry from purifying isotopes to delivering therapeutic doses to patients, Cotruvo said.

In addition to Cotruvo and Deblonde, the research team includes Joseph Mattocks, a graduate student at Penn State, and Ziye Dong, Paul Wooddy and Mavrik Zavarin at LLNL. The work is funded by LLNLs Laboratory Directed Research and Development program and the Department of Energy Office of Science.

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Radioactive metals for medicine get a boost from recently discovered protein | Penn State University - Penn State News

Biochemistry

Long-Time Professor of Biochemistry at URI, Joel A. Dain, Dies at 89 – GoLocalProv

Tuesday, August 24, 2021

Shalom Memorial Chapel

Joel was the caring and playful father of Peter J. Dain (Deborah Blicher), of Sudbury, MA; Jonathan L. Dain (Karen Kainer), of Gainesville, FL; and Leonard E. Dain (Ivetia Paniagua), of Seattle, WA. Joel was the dear brother of Martin Dain of Sun City, FL, and was the loving and mischievous grandfather of Rebekah, Beatrice, Kristina, Max, Joshua, and Isabel. He was a resident of Kingston since 1962.

Joel received his doctorate from Cornell University in 1956. He was a Professor of Biochemistry at URI for close to 60 years. After retiring in 2015, he continued working as an Emeritus Professor until his death. Joel was known for his influential research on the biochemical underpinnings of Tay-Sachs, diabetes, and other diseases, and for his caring and dedicated mentoring of numerous graduate students and postdocs with whom he maintained regular contact. From early on he opened his lab to female and male graduate students alike from all over the world and from diverse backgrounds. In addition to hisundergraduate and graduateteaching and research duties, he served on committees tasked with hiring University coaches, Athletic Directors, and Presidents.

Joel was an active member of various organizations that demonstrated his eclectic interests:

AAUP (American Association of University Professors)American Chemical Society (ACS) In 1995, he was elected chairman of the Rhode Island Section of the ACS.URI Athletic CouncilDemocratic Town CommitteeAmerican Philatelic Society

As a part of his professional work, Joel and Ellie took their family to live in locations as diverse as Heidelberg, Germany; Santa Rosa, California; and Tokyo, Japan, where he collaborated with scientists at local universities. He gave invited lectures at conferences and universities worldwide.

Joel and Ellie were also generous donors to numerous causes in support of human rights, scientific research, and the environment.

Sports were a very important part of Joels life. He was a runner in high school; he played junior varsity basketball at the University of Illinois; and into his 80s he was a regular at weekly pick-up basketball games at URIs Keaney Gym. He rarely missed a basketball game by his beloved URI Rams, and for almost 60 years was a fixture at Keaney Gym and then the Ryan Center. Joel was also a lifelong and ardent tennis player a love he passed on to his sons.

Joel was an avid reader and was particularly fond of suspense and detective novels. He was a regular at the Kingston Library.

Joel had a wry sense of humor which he applied to most any situation he encountered, particularly politics. He greatly enjoyed bantering with friends, family, colleagues, and acquaintances.

Joel was a lifelong stamp collector, reflecting his interest in all things international. For many years, he taught beginning stamp collecting to children through the Neighborhood Guild Community Center in South Kingstown.

Graveside services are open to the public and will be held Tuesday, August 24that 12:00 noon in New Fernwood Cemetery, 3102 Kingstown Rd., Kingston.

Due to the age and health of those attending, we ask that mourners please wear a mask and practice social distancing.

A private family gathering will be held after the service.

In lieu of flowers, contributions in Joels memory may be made to Beatrice Dain Memorial Fund in Diabetes. To make a gift, visiturifoundation.organd click theMake a Giftbutton in the upper right corner. Indicate the amount of your gift, then click select from a list of options. Scroll down to URI Programs and Initiatives and click Other Funds, then Continue. In the text box type Beatrice Dain Memorial Fundin Diabetes. Complete the form with the requiredinformationand follow the payment options.

Memorial gifts may also be made by check,payable to the URI Foundation & Alumni Engagement, and writing Beatrice Dain Memorial Fundin Diabetes in the memo line. Mail to: URI Foundation & Alumni Engagement, PO Box 1700, Kingston, RI 02881.

Contributions may also be made toMultiple Myeloma Research Foundation.

To attend the funeral service via Zoom, pleaseclick here.

Meeting ID: 849 3499 3118

Passcode: 548378

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Long-Time Professor of Biochemistry at URI, Joel A. Dain, Dies at 89 - GoLocalProv

Biochemistry

Wang Receives ASBMB Young Investigator Award | Newsroom – UNC Health and UNC School of Medicine

Greg Wang, PhD, associate professor of biochemistry and biophysics, has received the 2022 ASBMB Young Investigator Award.

Greg G. Wang, PhD, associate professor at the University of North Carolina School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center, has received the 2022 ASBMB Young Investigator Award, which recognizes outstanding research contributions to biochemistry and molecular biology and contributions to the community of scientists. Wangs lab studies how chromatin modification and epigenetic modifications contribute to gene regulation and cancer development.

The ASBMB Young Investigator Award (formerly the ASBMB/ScheringPlough Research Institute Award) recognizes outstanding research contributions to biochemistry and molecular biology. The recipient must have no more than 15 years postdoctoral experience. Nominations must be originated by society members, but nominees need not be ASBMB members.

The award consists of a plaque, $5,000, and transportation and expenses to present a lecture at the ASBMB annual meeting.

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Wang Receives ASBMB Young Investigator Award | Newsroom - UNC Health and UNC School of Medicine

Biochemistry

Biochemistry offers options to help reduce huge potato losses in the US – FreshPlaza.com

Massive losses in the number one US vegetable crop, potatoes, aren't only due to pests or drought, theyre due to damage in the handling and storage of potatoes over the nine months of storage they generally undergo on their way to the supermarket as fresh potatoes or as potato chips or fries.

A biochemistry approach that seeks to identify genetic characteristics of the wound healing process in potatoes has had success in a project led by Dylan Kosma, a biochemist in the College of Agriculture, Biotechnology & Natural Resources at the University of Nevada, Reno.

In his work, completed as part of the CollegesExperiment Stationresearch, Kosma has identified the first transcription factors known to regulate deposition of components that make up the skin that forms during the wound healing process in potatoes.

"We're working on protein transcription factors," he said. "You can think of transcription factors like the main switch in an electric panel or breaker box, with 15 circuits under control of the main switch. Finding the master switch and how it works to switch on the wound healing process in potatoes is key.

According to an article on unr.edu, One important component of potato tuber wound healing is the deposition of a corky material that makes up a large proportion of skin that covers wound sites, suberin. Suberin is a lipid polymer that is produced by all plants and is a major component of wound healing tissues in potatoes. While this wound-healing tissue can be found in nearly every plant, there is still relatively little known about its makeup and function. Even less is known about the genetic controls of wound suberin formation.

In addition to stemming the tide of losses with potatoes, Kosma hopes what they learn in this process will also be applicable to other food crops

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Biochemistry offers options to help reduce huge potato losses in the US - FreshPlaza.com

Biochemistry

FDA approval of belzutifan culminates 25-year journey at UTSW from gene discovery to a first-in-class drug – UT Southwestern

DALLAS Aug. 21, 2021 A first-in-kind kidney cancer drug developed from laboratory and translational studies conducted at UTSouthwestern Medical Center received approval from the Food and Drug Administration, providing a new treatment for patients with familial kidney cancer.

FDA approval of belzutifan culminates a 25-year journey at UTSW from gene discovery to a first-in-class drug.

Mercks belzutifan grew out of the discovery at UTSouthwestern of a protein,hypoxia-inducible factor 2-alpha(HIF-2), that is key to fuel the growth of kidney and other cancers. HIF-2 was discovered by Steven McKnight, Ph.D., Professor of Biochemistry.

This is an exciting milestone for patients with inherited forms of kidney cancer who are in need of more effective therapies, said David Russell, Ph.D., Vice Provost and Dean of Research, and Professor of Molecular Genetics, who collaborated in the early stages of the research.

The drug, once called PT2977, was developed based on a backbone discovered by UTSW researchers, with further drug development efforts conducted by a spinoff company named Peloton Therapeutics, which was launched on the UTSW campus and eventually acquired by Merck.

Drs. McKnight and Russell first identified HIF-2 in the 1990s.

HIF-2 was considered undruggable for many years until two more UTSW scientists at the time Richard Bruick, Ph.D., Professor of Biochemistry, and Kevin Gardner, Ph.D., Professor of Biophysics, who also directs a structural biology center at the City University of New York did the structural and biochemical work showing that the HIF-2 molecule contains a pocket that is potentially druggable. The two scientists then identified multiple compounds that fit into this pocket and inhibited the activity of HIF-2.

The history of belzutifans development demonstrates the value of cross-disciplinary collaborations at academic medical centers and how that can translate to new treatments for diseases, said Dr. Russell. It also underscores the value of investing in basic science discoveries at the core of advancements in medicine.

In 2011, several researchers spun off Peloton Therapeutics, and by 2019, when Merck acquired the company, at least three HIF-2 agents were under investigation.

James Brugarolas, M.D., Ph.D., Director of the UTSW Kidney Cancer Program

James Brugarolas, M.D., Ph.D., Director of the Kidney Cancer Program at UTSouthwesterns Harold C. Simmons Comprehensive Cancer Center, showed that the drug was effective against kidney cancer.

With funding from a prestigious National Cancer Institute SPORE award, they showed in a publication inNaturein 2016 that the drug was able to inhibit HIF-2in human kidney tumors transplanted into mice and stop their growth.

This and other studies led to the first clinical trial of PT2385, a precursor to PT2977, which became belzutifan. The trial, which was led by the UTSW Kidney Cancer Program, showed that the drug was well-tolerated and active.

The approval of belzutifan represents a new paradigm in the treatment of kidney cancer, said Dr. Brugarolas, Professor of Internal Medicine. By exclusively targeting HIF-2, which is essential for kidney cancers but dispensable for normal processes, belzutifan specifically disables cancer cells while sparing normal cells. Belzutifan is the best-tolerated kidney cancer drug today and one suitable for patients with familial kidney cancer. It is a testament to the prowess of designer drugs and carefully chosen targets of which it is a prime example.

1997UTSouthwestern biochemist Steven McKnight, Ph.D., and molecular geneticist David Russell, Ph.D., report the discovery of the HIF-2 gene, which they call EPAS1. The team shows that HIF-2 binds to another protein, HIF-1. The HIF-2 partner functions like a pair of tweezers to grab DNA. HIF-2 binds DNA at specific places to initiate the production of other proteins such as VEGF, which support kidney cancer growth.

2003The laboratories of Richard Bruick, Ph.D., and Kevin Gardner, Ph.D., uncover aspects of the atomic blueprint of HIF-2. They show how HIF-2 docks with HIF-1 to assemble into a functional HIF-2 complex. They identify a cavity within the HIF-2 protein, hypothesizing that it may offer a foothold for a drug. Working with UTSouthwesterns High-Throughput Screening laboratory, Drs. Bruick and Gardner develop a test to identify chemicals among 200,000 drug-like molecules that bind to the HIF-2 cavity, preventing HIF-2 binding to HIF-1. By interfering with HIF-2 binding to HIF-1, these compounds block HIF-2 action. The most promising chemicals undergo a refinement process by medicinal chemists at UTSouthwestern.

2010Peloton Therapeutics is founded by UTSW researchers to develop the HIF-2 blocking chemicals into drugs. Peloton scientists create libraries of related compounds, ultimately identifying PT2385 and PT2977 to test in humans. A related drug, PT2399, is identified for laboratory work.

2016Dr. James Brugarolas validates HIF-2 as a target in kidney cancer. In experiments incorporating more than 250 mice transplanted with human kidney tumors, researchers show that PT2399 blocks HIF-2 while not affecting related proteins, is active against 50% of human kidney tumors, and has more activity and is better tolerated than sunitinib (the most commonly used drug for renal cancer treatment at the time).

2018Dr. Kevin Courtney reports the results of a phase 1 clinical trial testing PT2385 in humans. The trial represents the first-in-human study of a first-in-class inhibitor of HIF-2. The trial, which involves 51 patients, shows that PT2385 is safe, well tolerated, and active against kidney cancer in humans. More than 50% of patients see their cancer regress or stabilize.

2019U.S. drug manufacturer Merck acquires Peloton Therapeutics for $1.05 billion, with an additional $1.15 billion contingent on sales and regulatory milestones.

2020Through studies of tumor biopsy samples from patients who participated in the Phase 1 clinical trial, Drs. Courtney, Brugarolas, and Ivan Pedrosa report the identification of drug resistance mutations in patients, establishing HIF-2 as the first-known core dependency of kidney cancer.

Dr. Brugarolas holds The Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Dr. McKnight holds the Distinguished Chair in Basic Biomedical Research. Dr. Pedrosa holds the Jack Reynolds, M.D., Chair in Radiology. Dr. Russell holds the Eugene McDermott Distinguished Chair in Molecular Genetics. Disclosures: UTSouthwestern and some of its researchers will receive financial compensation, through prior agreements with Peloton, based on belzutifans FDA approval.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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FDA approval of belzutifan culminates 25-year journey at UTSW from gene discovery to a first-in-class drug - UT Southwestern

Biochemistry

New study examines ‘Achilles heel’ of cancer tumours, paving the way for new treatment strategies – UBC Faculty of Medicine

Researchers at UBCs faculty of medicine and BC Cancer Research Institute have uncovered a weakness in a key enzyme that solid tumour cancer cells rely on to adapt and survive when oxygen levels are low.

The findings, published today in Science Advances, will help researchers develop new treatment strategies to limit the progression of solid cancer tumours, which represent the majority of tumour types that arise in the body.

Solid tumours rely on blood supply to deliver oxygen and nutrients to help them grow. As the tumours advance, these blood vessels are unable to provide oxygen and nutrients to every part of the tumour, which results in areas of low oxygen. Over time, this low-oxygen environment leads to a buildup of acid inside the tumour cells.

To overcome this stress, the cells adapt by unleashing enzymes that neutralize the acidic conditions of their environment, allowing the cells to not only survive, but ultimately become a more aggressive form of tumour capable of spreading to other organs. One of these enzymes is called Carbonic Anhydrase IX (CAIX).

Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their Achilles heel. By inhibiting its activity, we can effectively stop the cells from growing, explains the studys senior author Dr. Shoukat Dedhar, professor in UBC faculty of medicines department of biochemistry and molecular biology and distinguished scientist at BC Cancer.

Dr. Dedhar and colleagues previously identified a unique compound, known as SLC-0111currently being evaluated in Phase 1 clinical trialsas a powerful inhibitor of the CAIX enzyme. While pre-clinical models of breast, pancreatic and brain cancers have demonstrated the effectiveness of this compound in suppressing tumour growth and spread, other cellular properties diminish its effectiveness.

In this study, the research team, which included Dr. Shawn Chafe, a research associate in Dr. Dedhars lab, together with Dr. Franco Vizeacoumar and colleagues from the University of Saskatchewan, set out to examine these cellular properties and identify other weaknesses of the CAIX enzyme using a powerful tool known as a genome-wide synthetic lethal screen. This tool looks at the genetics of a cancer cell and systematically deletes one gene at a time to determine if a cancer cell can be killed by eliminating the CAIX enzyme together with another specific gene.

According to Dr. Dedhar, the results of their examination were surprising and point to an unexpected role of proteins and processes that control a form of cell death called ferroptosis. This form of cell death happens when iron builds up and weakens the tumours metabolism and cell membranes.

We now know that the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis, says Dr. Dedhar. Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumor growth.

There is currently a large international effort underway to identify drugs that can induce ferroptosis. This study is a major step forward in this quest.

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New study examines 'Achilles heel' of cancer tumours, paving the way for new treatment strategies - UBC Faculty of Medicine

Biochemistry

Eight receive excellence awards as academic year opens – uwec.edu

University of Wisconsin-Eau Claire Chancellor James Schmidt honored eight faculty and staff members for their excellence during the Blugold Breakfast and academic year opening meeting on Aug. 24.

Recipients of UW-Eau Claire's 2021 excellence awards are, from left, Rob Mattison, Signe Matson, Dr. Jeanette Olsen, Kris Presler, Dr. Sanchita Hati, Dr. Rose-Marie Avin, Dr. Pam Forman and Dr. Heather Ann Moody.

The chancellor recognized the following 2021 award winners:

Each award recipient received a university medallion and $1,500. All of the UW-Eau Claire Foundation excellence awards for faculty and staff are funded by Markquart Motors and Markquart Toyota of Eau Claire. The award honoring the 2021 UW System Board of Regents Excellence in Teaching Award nominee is funded by the Arnold and Lois Domer Foundation of Eau Claire.

Dr. Rose-Marie Avin, professor of economics and director of the Womens, Gender and Sexuality Studies program, received the Excellence in Equity, Diversity and Inclusion Award.

Avin has demonstrated a sincere commitment to equity, diversity and inclusion during her 34 years at UW-Eau Claire through outstanding service and teaching, according to her nomination materials.

Dr. Avins entire lifes work has been dedicated to EDI, nominators say. Her advocacy on behalf of EDI is global and transnational.

Through her courses and immersion programs, Avin taught students to advocate for gender, racial and economic justice in the U.S. and other nations such as Nicaragua, Spain, Vietnam, India, Brazil and Argentina.

Avin has included UW-Eau Claire students in her work to fight racism, sexism, homophobia and xenophobia in the world.

You have showed me that the world is so many shades of gray, a student wrote in a letter to the WGSS program. I cannot express in words how appreciative of this I am. It is impossible.

Dr. Pam Forman, professor and chair of the sociology department and a faculty member in the Office of Research and Sponsored Programs.

Students select the Excellence in Advising Award, and Blugolds say Forman, who has been at UW-Eau Claire for 17 years, always takes time for them, even when she is running in multiple directions.

The sociology students who Forman advises describe her as unmatched in empathy, passion for application of sociology in real-world contexts and commitment to students.

Forman promotes an inclusive campus by updating sociology students about current events and extending her expertise to all.

As a department chair, Dr. Forman is exceptional, nomination documents state. As an advisor, Dr. Forman consistently goes above and beyond. As an ally to all students, Dr. Forman is unmatched.

Dr. Sanchita Hati, professor of chemistry and biochemistry, received the Excellence in Scholarship Award.

Hati, who has been at UW-Eau Claire for 15 years, is a productive researcher who has an exemplary publication record with undergraduate students, according to nomination materials. Her students have presented at least one poster at the national meeting of the American Chemical Society every year since 2014.

She has moved research into the teaching laboratory and, in some classes, all students in her upper-level biochemistry courses have become authors on a peer-reviewed publication, according to the nomination materials. Her peers in science recognize her as an outstanding scholar.

Hati currently manages three distinct projects: exploring protein dynamics to design the next generation of antibiotics, developing a noninvasive tool for cancer diagnostics in collaboration with Mayo Clinic and investigating the role of oxidative stress on the severity of COVID-19 infections.

Beyond direct contributions to science, Dr. Hati is also an outstanding role model who encourages students to become independent, lifelong learners, according to nomination materials. She has directly mentored 50 undergraduates in her research group, and about half of these students have entered Ph.D. programs, including many at prestigious universities like Dartmouth and Northwestern.

Rob Mattison, senior information systems and technology services videographer in Learning and Technology Services, received the University Staff Excellence in Service Award.

Mattison, who has been at UW-Eau Claire for nine years, shows respect to all members of the university community and has a genuine goal to brighten the day of people he encounters, according to nomination materials.

Rob routinely goes above and beyond his job duties to assist faculty in creating engaging video content for courses, according to nomination materials. This was especially true in 2020 as Rob worked long days preparing courses and content for virtual learning. Many of the courses offered on this campus are made better through Robs efforts.

Mattison is a consummate professional, according to nomination materials, who strives for high-quality work while maintaining a casual, friendly, funny and enthusiastic demeanor. He cares about the well-being of students and considers his co-workers to be family.

Rob is an example of what excellence means at UWEC, according to nomination materials. He puts more effort into his job than anyone could ask while living his dream and is supportive of everyone and their dreams.

Signe Matson, lead academic advisor in the Advising, Retention and Career Center, received the Academic and Professional Staff Excellence in Service Award.

Matson, who has been at UW-Eau Claire for 21 years, has been the lead advisor in the arts and humanities cluster since the formation of the Advising, Retention and Career Center in 2016. Students have appreciated Matsons support over the years.

Signe is a very kind and caring advisor! one nominator states. She has provided a lot of helpful information and guidance as I consider a degree at UWEC while taking courses as a special student. Going back to school as a nontraditional student is a bit intimidating, but Signe has been full of encouragement and helped break down the steps in a clear and understandable manner.

Matson has helped with training and mentoring new staff members, and is a steady and reliable team member who has a wealth of institutional knowledge, according to nomination materials. Matson is considered a hard-working, compassionate and student-first person who is a great resource inside and outside ARCC.

Signes knowledge of campus resources, advising experience, calm professional demeanor and positive attitude make collaborating with her in this work a delight, according to nomination papers. I trust Signe to serve our students while holding true to the mission of the university.

Dr. Heather Ann Moody, associate professor of American Indian studies, received the Faculty Excellence in Service Award.

Moody, who has been at UW-Eau Claire for 14 years, is a true example of a servant leader with a passion for undergraduate education and mentorship, commitment to EDI and extensive service beyond campus, according to nomination materials. In 2019, Moody received an Outstanding Women of Color in Education Award from the UW System.

Dr. Moodys professional service to the greater Eau Claire community and to the state of Wisconsin reflects the values of this university and embodies the spirit of the Excellence in Service Award, according to nomination materials.

Moody has been instrumental in leading important EDI initiatives at UW-Eau Claire. She is a co-chair of the EDI Strategic Plan Committee that will guide the institution for the next five years and also co-chairs the Center for Racial and Restorative Justice Implementation Committee.

Dr. Moody is a model faculty member in her dedication and willingness to provide service to both our university and surrounding communities, according to nomination materials. She exemplifies what service means and does so with great knowledge, care and enthusiasm. Dr. Moody goes above and beyond in her service to support the growth of knowledge and understanding on the UWEC campus related to the Native American people within Wisconsin.

Dr. Jeanette Olsen, assistant professor and director of assessment and evaluation in the College of Nursing and Health Sciences, received the Excellence in Teaching Award.

Olsen, who has been at UW-Eau Claire for five years, was praised in nomination materials for her dedication to students and her ability to provide multiple methods of learning to accommodate every type of student. Students say Olsen takes a genuine interest in the lives of those in her classroom.

She always has time to answer questions and is willing to take the time to make sure you understand it, student nominators say. If you don't, she will find a different way to teach it. Even though she has students for just one semester, she knows and remembers everyone's name. She makes you feel important. She makes every question feel valid and is excited to help foster a growth of knowledge.

Olsen is extremely knowledgeable and approachable, always has a smile on her face and she truly cared about us as her students and wanted us to do well and succeed as nurses.

Dr. Olsen greatly encouraged me and my classmates in the nursing program to achieve our fullest potential, a student says. She remains an inspiration to me and is someone I hope to emulate in my nursing career.

Kris Presler, a professor of mathematics, was UW-Eau Claires nominee for the UW System Board of Regents Excellence in Teaching Award.

Presler, who has been at UW-Eau Claire for 18 years, helps his students realize that mistakes are just opportunities for learning that should be embraced and not feared, according to nomination materials.

Presler is described as a true professional who is full of humility and grace, valuing the people he serves each day. He works to bring humor into his courses to produce a more engaged classroom environment where laughter leads to a greater approachability, approachability to questions and questions to understanding.

Students praise Presler for his professional mentorship and advising in technical upper-level courses.

Actuaries often excel at math but struggle to clearly communicate their ideas and analysis with others, nominators say. Kris actuarial science curriculum was mathematically challenging and prepared students for exams, but also placed a heavy emphasis on creating well-rounded, articulate actuaries.

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Eight receive excellence awards as academic year opens - uwec.edu