#Dana-Farber Cancer Center

[tracychamberlainhigginbotham]

(via Monday Motivation: "It's for Them, Not Me")

[covid-safer-hotties]

Controversy Over Cancer Center Masking Policies as COVID Surge Looms? - Published Aug 27, 2024

By: Marcia Frellick

Although oncologists broadly agree that people with cancer have an elevated risk for COVID-19 infection, long COVID, breakthrough infections, and hospitalization, the nation’s top cancer centers are sharply divided on masking policies, even when the virus is surging, new data show.

Michael Hoerger, PhD, MSCR, a clinical health psychologist at Tulane Cancer Center in New Orleans, Louisiana, who models COVID transmissions, said that he and colleagues were concerned about the lack of protections in public places three years after the start of the pandemic. They looked to National Cancer Institute–designated cancer centers to gauge what top institutions were doing to protect immunocompromised patients in the winter of 2023–2024, when the United States experienced its second-highest COVID transmission peak. The highest peak was in the winter of 2021–2022, with the surge of the BA.1 Omicron subvariant, Dr. Hoerger said.

The researchers analyzed each center’s policies on Jan. 15, 2024, the day they had estimated to be the midpoint of the surge. They found that all 67 of the patient-serving centers had COVID-19 policies. However, only 28 centers (41.8%) required universal masking for all visitors and staff in at least some clinical areas, and only 12 centers (17.9%) required universal masking in all areas. The findings were published in JAMA Network Open.

Compared with what the rest of the country was doing at the time, Dr. Hoerger said, the results from the select cancer centers were “encouraging.” Although no national study has compared all masking policies, “I would guess less than 5% of hospitals had any sort of masking requirement,” he said.

“I would encourage people to view universal masking as an indicator of healthcare quality when there’s a COVID wave. This shows that many of the top cancer centers in the country are aware of that.”

Centers with strict masking guidelines signal to patients that COVID is still a serious disease and that people with cancer should take extra precautions, Dr. Hoerger said. Those guidelines should also signal to other cancer centers that they may want to rethink their policies, he added.

Although many people refer to COVID in the past tense, spikes in incidence keep coming. “We’re experiencing a wave right now,” Dr. Hoerger noted. “Right now, the South and West are having the highest transmission, and probably the peak will happen for the Midwest and Northeast a little bit later, like early September. Our model, based on wastewater, is that over a million Americans are getting infected each day.”

Dana-Farber Cancer Institute confirmed that it was one of the 12 centers that required universal masking in all areas on the Jan. 15 date. “This policy not only helped to protect our patients but also the visitors and the workforce,” said Meghan A. Baker, MD, ScD, the hospital epidemiologist at the institute.

As for the near future, she said Dana-Farber will follow state guidance and monitor local viral respiratory illness, “and will consider reinstating a mask requirement to coincide with the peak of the viral respiratory season.”

At the University of Texas MD Anderson Cancer Center in Houston, Chief Infection Control Officer Amy Spallone, MD, said that during the past winter surge, the institution required staff, visitors, and patients to wear masks in designated areas and required masking in all locations for symptomatic people. “The institution will continue these practices this coming respiratory viral season and adjust as needed, based on the available evidence,” she said.

Leo David Wang, MD, PhD, associate professor of pediatrics and immuno-oncology at City of Hope National Medical Center in Duarte, California, said that he was not surprised by the widely varying masking policies in the study, given the rapidly changing nature of the virus. He added that it would be important to know the COVID prevalence rates in a particular area on the designated date to better understand the individual policies at work. City of Hope had a universal masking policy until very recently, and still requires masking in some spaces, he said.

Dr. Wang, who performs stem cell transplants, has always masked when interacting with patients, even before COVID. “It doesn’t bother me, and I don’t think it bothers my patients.” He said that oncologists are well aware of the vulnerability of their patients and that part of an oncologist’s responsibility is to maximize patients’ safety.

“At the same time,” he says, “It’s also our responsibility to incorporate evidence-based practices so our patients aren’t facing undue restrictions.”

Study link:  jamanetwork.com/journals/jamanetworkopen/fullarticle/2821699

[bpod-bpod]

Gastric Balance

Characterising the cells and signals involved in maintaining the balance between self-renewal and differentiation of stem cells of the stomach

Read the published research article here

Image from work by Elisa Manieri and colleagues

Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, December 2023

You can also follow BPoD on Instagram, Twitter and Facebook

[amatrudalab]

Meet the Amatruda Lab!

James Amatruda, MD, PhD

www.chla.org

Dr. James Amatruda is the Head of Basic and Translational Research for the Cancer and Blood Disease Institute at Children’s Hospital Los Angeles. He’s the inaugural holder of the Dr. Kenneth O. Williams Chair in Cancer Research. Dr. Amatruda is a Professor of Pediatrics and Medicine for the Keck School of Medicine of USC. He attends on the Solid Tumor oncology service at CHLA.

Dr. Amatruda received his MD and PhD from Washington University School of Medicine. He completed his internship and residency in Internal Medicine from Brigham and Women’s Hospital. He was a Visiting Fellow at the Institute of Cell Biology in Consiglio Nazionale delle Ricerche in Rome and completed his Medical Oncology fellowship at Dana-Farber/Partners Cancer Care in Boston, Massachusetts.

When not in the lab, Dr. Amatruda enjoys running, reading, music-making and exploring around Los Angeles.

Ashley Jean, MD

www.chla.org

Dr. Ashley Jean is a Clinical Fellow in the Amatruda Lab. Dr. Jean graduated from Tufts Medical School in Boston and completed her Pediatric Residency at Maine Medical Center. Dr. Jean started her Pediatric Fellowship at Children’s Hospital Los Angeles in 2019.

Her research focuses on pediatric Ewing Sarcoma. She is currently studying the TAK1 pathway in the tumor genesis of this condition.

Dr. Jean likes to spend her free time outdoors. She enjoys activities such as hiking, paddle boarding and snowboarding.

Christopher Kuo, MD

www.chla.org

Dr. Christopher Kuo is a Clinical Fellow in the Amatruda Lab. Dr. Kuo received his Medical Degree from Rush University and completed his Pediatric Residency from Children’s Hospital Los Angeles. Dr. Kuo started his Pediatric Fellowship at Children’s Hospital Los Angeles in 2020.

His research interest is in osteosarcoma. He is currently working on a project that involves the investigation of the tumor microenvironment of Ewing sarcoma.

Dr. Kuo’s hobbies include breakdancing, swimming and going to coffee shops.

Adam Marentes, MSc., PhD Candidate

www.chla.org

Adam Marentes is a Graduate Student Researcher in the Amatruda Lab. Adam received his Bachelor of Science in Neuroscience from the University of California, Riverside. He then completed his Master of Science from California Polytechnic University Pomona. Adam is currently attending University of Southern California Keck School of Medicine to earn his PhD in Cancer Biology and Genomics.

Adam’s research focus is in mitochondrial DNA variants in Ewing Sarcoma. He is currently working on a collaboration that involves editing mitochondrial DNA in cancer cell lines in zebrafish.

Adam enjoys baking, playing video games with his fiancé and catching a show at the local comedy club.

Tanya Mosesian, MHA

www.chla.org

Tanya Mosesian received her Bachelor of Science in Public Health from California State University of Northridge. She then completed her Master of Health Administration at the University of Southern California.

Tanya is Project Associate for the Amatruda Lab. She provides on-site support for all administrative matters and project facilitation.

Tanya enjoys spending time with her family and friends. She likes to play tennis and hike during the weekends.

Elena Vasileva, PhD, MSc.

www.chla.org

Dr. Elena Vasileva is a post-doctoral fellow in the Amatruda Lab. Dr. Vasileva received her Bachelor of Science and Master of Science from Peter the Great St. Petersburg Polytechnic University in Applied Mathematics and Physics. She received her PhD in Molecular Biology from the Institute of Cytology, Russian Academy of Sciences.

Dr. Vasileva is interested in studying the molecular mechanisms of cancer development and progression. She has developed an inducible zebrafish model of EWS-FLI driven Ewing Sarcoma as a platform for biologic discovery and preclinical testing of novel therapies.

Dr. Vasileva enjoys running and hiking in Los Angeles.

Mona Wu, PhD

www.chla.org

Dr. Mona Wu is a post-doctoral fellow in the Amatruda Lab. Dr. Wu received her Bachelor of Science from the University of British Columbia, a Master of Science from Université de Montréal, and a PhD from McGill University.

Dr. Wu is interested in understanding the cell of origin for pediatric neoplasms because she believes that this knowledge could lead to better early biomarkers and more effective treatment. She is particularly interested in understanding how aberrant ncRNA (especially miRNAs) may play a role in pediatric disease.

Dr. Wu likes reading and visiting different libraries. She enjoys “foodie-related” activities including trying restaurants, cooking, baking and watching (far too many) cooking shows.

[jcmarchi]

Seven with MIT ties elected to National Academy of Medicine for 2024

New Post has been published on https://thedigitalinsider.com/seven-with-mit-ties-elected-to-national-academy-of-medicine-for-2024/

Seven with MIT ties elected to National Academy of Medicine for 2024

The National Academy of Medicine recently announced the election of more than 90 members during its annual meeting, including MIT faculty members Matthew Vander Heiden and Fan Wang, along with five MIT alumni.

Election to the National Academy of Medicine (NAM) is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.

Matthew Vander Heiden is the director of the Koch Institute for Integrative Cancer Research at MIT, a Lester Wolfe Professor of Molecular Biology, and a member of the Broad Institute of MIT and Harvard. His research explores how cancer cells reprogram their metabolism to fuel tumor growth and has provided key insights into metabolic pathways that support cancer progression, with implications for developing new therapeutic strategies. The National Academy of Medicine recognized Vander Heiden for his contributions to “the development of approved therapies for cancer and anemia” and his role as a “thought leader in understanding metabolic phenotypes and their relations to disease pathogenesis.”

Vander Heiden earned his MD and PhD from the University of Chicago and completed  his clinical training in internal medicine and medical oncology at the Brigham and Women’s Hospital and the Dana-Farber Cancer Institute. After postdoctoral research at Harvard Medical School, Vander Heiden joined the faculty of the MIT Department of Biology and the Koch Institute in 2010. He is also a practicing oncologist and instructor in medicine at Dana-Farber Cancer Institute and Harvard Medical School. 

Fan Wang is a professor of brain and cognitive sciences, an investigator at the McGovern Institute, and director of the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics at MIT.  Wang’s research focuses on the neural circuits governing the bidirectional interactions between the brain and body. She is specifically interested in the circuits that control the sensory and emotional aspects of pain and addiction, as well as the sensory and motor circuits that work together to execute behaviors such as eating, drinking, and moving. The National Academy of Medicine has recognized her body of work for “providing the foundational knowledge to develop new therapies to treat chronic pain and movement disorders.”

Before coming to MIT in 2021, Wang obtained her PhD from Columbia University and received her postdoctoral training at the University of California at San Francisco and Stanford University. She became a faculty member at Duke University in 2003 and was later appointed the Morris N. Broad Professor of Neurobiology. Wang is also a member of the American Academy of Arts and Sciences and she continues to make important contributions to the neural mechanisms underlying general anesthesia, pain perception, and movement control. 

MIT alumni who were elected to the NAM for 2024 include:

Leemore Dafny PhD ’01 (Economics);

David Huang ’85 MS ’89  (Electrical Engineering and Computer Science) PhD ’93 Medical Engineering and Medical Physics);

Nola M. Hylton ’79 (Chemical Engineering);

Mark R. Prausnitz PhD ’94 (Chemical Engineering); and

Konstantina M. Stankovic ’92 (Biology and Physics) PhD ’98 (Speech and Hearing Bioscience and Technology)

Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, the National Academy of Medicine addresses critical issues in health, science, medicine, and related policy and inspires positive actions across sectors.

“This class of new members represents the most exceptional researchers and leaders in health and medicine, who have made significant breakthroughs, led the response to major public health challenges, and advanced health equity,” said National Academy of Medicine President Victor J. Dzau. “Their expertise will be necessary to supporting NAM’s work to address the pressing health and scientific challenges we face today.” 

[shinboardnet]

제목: AI와 암 치료의 조화: 혁신의 신호탄을 쏘아 올리다 --- 암 치료 분야에서 놀라운 혁신이 이루어지고 있습니다. 미래의 가능성으로만 여겨

AI와 암 치료: 새로운 혁신의 시대가 열리다 인공지능(AI)이 암을 치료할 수 있을까요? 이는 미래의 희망뿐만 아니라 현실로 다가오는 가능성입니다. 최근 시애틀에 위치한 프레드 허치 암 연구소(Fred Hutch Cancer Center)를 중심으로 4개의 주요 암 연구 기관들이 AI를 통해 암과의 싸움에서 혁신적인 길을 여는 'Cancer AI Alliance'를 결성했습니다. 기술과 ��료의 만남: 암을 이기기 위한 힘 프레드 허치 암 연구소, 다나 파버 암 연구소(Dana Farber Cancer Institute), 메모리얼 슬론 케터링 암 센터(Memorial Sloan Kettering Cancer Center), 그리고 존스 홉킨스 시드니 키멜 포괄암센터(Sidney Kimmel…

[sa7abnews]

What to Expect at a Colonoscopy

New Post has been published on https://sa7ab.info/2024/08/16/what-to-expect-at-a-colonoscopy/

What to Expect at a Colonoscopy

If you’ve been putting off a colonoscopy, you’re not alone. The fasting is uncomfortable, the prep is disagreeable, and the procedure itself requires you to be put to sleep. But colonoscopies are more than worthwhile, since they’re the gold standard for detecting colon cancer. 

So who should schedule a colonoscopy, and what can you expect from the procedure? Dr. Meir Salama, chief of gastroenterology at St. Joseph’s Medical Center in Yonkers, N.Y., explains what to know to get the most out of this potentially life-saving tool.

Who should be tested?

The answer to that question is simple: everyone. This year, more than 106,000 Americans will develop colon cancer, according to the American Cancer Society. Since the mid-1990s, rates have been increasing by 1% to 2% per year in people younger than 55. Nobody is immune to colon cancer and no one, therefore, should pass up this critical precaution. 

Just when you should start is another matter. Salama says screening for most men and women should begin at age 45 and be repeated every 10 years up to and including age 75.

Read More: The 1 Heart-Health Habit You Should Start When You’re Young

But those general rules don’t apply to everyone. Only lower-risk people—those without a first-degree family member who has had colon cancer, or people who haven’t before been diagnosed with intestinal polyps—should follow that schedule. First-degree family members are mothers, fathers, brothers, and sisters. If one of those relatives has or has had the disease, currently or in the past, you should start screening at age 40, or 10 years before the age at which your youngest family member with the disease was diagnosed—whichever is earlier, according to Salama and guidelines from the Dana-Farber Cancer Institute.

“So if your relative was diagnosed at age 50,” says Salama, “we would start looking at you at age 40.”

How do you prepare for a colonoscopy?

This is the part of the procedure that most people find at least a little unpleasant—and not without reason. The day before your colonoscopy, you can have a normal breakfast, but after that you have to limit your diet to clear liquids like broth and clear fruit juices, Salama says. Starting at 3:00 or 4:00 in the afternoon, you will begin drinking a laxative fluid your doctor will prescribe, and continue until about 7:00 pm. This will cause you to empty your bowels quite completely, within as little as an hour. But food that has not yet made it down to your large intestines will still be in your system. For this reason, it is best to repeat the laxative procedure the next morning, four or five hours before the test, Salama says. The laxative is typically made of polyethylene-glycol, a large molecule that is not absorbed by the bowel, along with electrolytes to prevent dehydration. Some cramping is possible as the bowels begin to empty.

“Recent studies suggest that a better bowel cleansing will be achieved with a split-dose preparation,” says Salama. “This will ensure a much more thorough cleansing than if you only did it the day before.”

What should you expect during the procedure?

The actual colonoscopy is the easiest part of the process, since you will be unconscious for it. An anesthesiologist or nurse anesthetist will typically administer the anesthetic propofol, which is a fast-acting drug that will knock you out immediately, but keep you out for only 15 minutes or so, says Salama.

For most colonoscopies, this is enough time. In a healthy person, a probe called a colonoscope will be inserted five to six feet into the large intestine. If you have a history of inflammatory bowel disease (IBD), like Crohn’s disease, the doctor may want to probe further, into the small intestine. This may also be the case if you have a family history of colon cancer or a personal history of polyps, Salama explains.

Read More: 7 Metrics Everyone Should Know About Their Own Health

If no polyps are found, your doctor will be able to give you the all clear once you wake up. If polyps are found, the colonoscopy may take up to 45 minutes. The polyps will be removed during the procedure and sent to a lab for a biopsy; the results may be back in as little as a day. If you have a broad, flat polyp which is harder to remove, your doctor may send you to a sub-specialist with more advanced surgical skills and tools. 

“Polyps are pre-malignant by virtue of their nature,” says Salama, “unless they were what’s called hyperplastic polyps, which are benign growths.” 

Removal of even a pre-malignant polyp will usually be a sufficient treatment. Only in more advanced cases—when an actual malignancy is detected via colonoscopy and biopsy—will more-extensive surgery and chemotherapy be in order. More than 99% of colon-cancer cases begin with a polyp, Salama says.

What follow-ups are required if you don’t have cancer but do have polyps?

Even if your polyp can be treated simply by removing it, your doctor may still want to see you more frequently than just once every 10 years. “It all depends on the histologic results of the pathology,” says Salama. “What is found? What kind of polyp is it? How large is it? That will determine when you come back. It could be three to six months, it could be a year. It could be three years, five years. It depends on what they find.”

Are there alternatives to colonoscopies?

Despite the development of other similar options, nothing is quite as comprehensive as the colonoscopy. Cologuard, a mail-in home stool test that checks for abnormal DNA in feces, is best for people who simply will not submit to a colonoscopy, Salama says, or who shouldn’t have it due to underlying conditions that make sedation dangerous.

The problem is, if abnormal DNA is detected, a colonoscopy is required to confirm the finding—and with a false positive rate of about 14% for home tests, people may wind up having the more invasive procedure anyway.

Read More: Do You Really Store Stress in Your Body?

Home tests, Salama says, “provide you a second-choice screening option, but if it comes back positive, you have to have a colonoscopy.”

In July, the U.S. Food and Drug Administration approved a blood test that similarly detects colon-cancer-related DNA, but the test is most effective at finding late-stage cancers. What’s more, its overall success rate is only 83% in uncovering cancer—which means a lot of cancers could still slip through—and 13% at spotting early-stage polyps. And, as with Cologuard, a positive test requires a colonoscopy to determine the location of the polyps and how advanced they are.   

Can everyone stop screening at age 75?

The 75-year-old cutoff date applies only to low-risk people with no first degree relatives with cancer and no history of polyps. People in higher-risk groups should continue being screened as their doctor recommends. Even people who are healthy may want to continue colonoscopies past 75, especially if they have a family history of living into their eighties or nineties or beyond.

“The longer you live, the more likely you’re going to develop a cancer,” Salama says. “If I have a very healthy patient who has very few comorbid problems—no heart disease, no lung disease—and tells me that his parents lived to 90 or 100,  if they want a colonoscopy, I go ahead and do it.”

[crimsonpublisherscancerstudy]

Nutrient Deprivation: A Cancer Treatment of Last Resort_Crimson Publishers

Opinion

A West Hartford high school senior was diagnosed with brain cancer, “a high-grade glioma.” Her parents brought her to Dana Farber Institute in Boston Massachusetts seeking the world’s best treatment. They took an apartment in Boston to support her through the ordeal. The patient received surgery and radiation, and, at five months after diagnosis, showed improvement, but, at seven months, relapsed. She received more surgery and radiation but died nine months after diagnosis [1]. It’s a tragic horror story that plays out in this way for some 3,000 young and many more, older adults each year. The patient’s parents did all they could to get their daughter the best treatment. But, in the end, it was inadequate. And it would have been inadequate at any cancer center. There simply is no dependable treatment for end-stage glioma. “Clearly, there exists an unmet need for innovative approaches” [2].

Read more about this article:

For more articles in Novel Approaches in Cancer Study

[pmcmarty]

Juneteenth, One Way to Commemorate…

What is "Juneteenth" you might be asking yourself?

Juneteenth is a Federal Holiday also called Emancipation Day, Freedom Day or Jubilee Day, Juneteenth is the commemoration of June 19, 1865, the day enslaved African Americans in Galveston, TX, learned that they were free.

For many who are reading this, you may not have a direct connection to the events that happened on June 19th, 1865. “How”, you may ask, “can I help commemorate this new holiday?”

One way to commemorate this is to help the Dana-Farber Cancer Institute address the disparities that many underserved groups, including Black Americans and those of low socioeconomic status, face when battling cancer.

Dr. Christopher Lathan, MD, MS, MPH is the Chief Clinical Access and Equity Officer at Dana-Farber Cancer Institute is leading efforts to address these disparities.

Dr. Lathan leads system-wide efforts to combat structural racism and improve health care outcomes for all patients and communities served by Dana-Farber by implementing new initiatives to reduce disparities in access to care. Dr. Lathan also partners with community and local leaders to address common challenges, such as health equity, social justice, and racism.

From Dr. Lathan's Profile on the Dana-Farber / Harvard Cancer Center site

To help fund Dr. Latham's research at Dana-Farber please consider making a donation.

100% of every donation goes directly to the Dana-Farber Cancer Institute in Boston and supports cancer research & patient care, including the efforts by Dr. Lathan to reduce cancer disparities and broaden access to high-level, quality care for vulnerable populations.

Click here to make $25 donation

Click here to make a $50 donation

Click here to make a $100 donation

Click here to make a $250 donation

Click here to make a $500 donation

Click here to make a $1,000 donation

Click here to make a donation of any other amount

Click here to donate using your Fidelity Donor Advised Fund

Thank you for your support!

Marty Middelmann

My 2024 Fundraising Goal: $12,000

Raised for 2024: $3,877

Number of Donors: 48

Corporate Matches: $350 (Including $100 Pending) 

My Progress Towards that Goal: 32.3%

[sunaleisocial]

“Rosetta Stone” of cell signaling could expedite precision cancer medicine

New Post has been published on https://sunalei.org/news/rosetta-stone-of-cell-signaling-could-expedite-precision-cancer-medicine/

“Rosetta Stone” of cell signaling could expedite precision cancer medicine

A newly complete database of human protein kinases and their preferred binding sites provides a powerful new platform to investigate cell signaling pathways.

Culminating 25 years of research, MIT, Harvard University, and Yale University scientists and collaborators have unveiled a comprehensive atlas of human tyrosine kinases — enzymes that regulate a wide variety of cellular activities — and their binding sites.

The addition of tyrosine kinases to a previously published dataset from the same group now completes a free, publicly available atlas of all human kinases and their specific binding sites on proteins, which together orchestrate fundamental cell processes such as growth, cell division, and metabolism.

Now, researchers can use data from mass spectrometry, a common laboratory technique, to identify the kinases involved in normal and dysregulated cell signaling in human tissue, such as during inflammation or cancer progression.

“I am most excited about being able to apply this to individual patients’ tumors and learn about the signaling states of cancer and heterogeneity of that signaling,” says Michael Yaffe, who is the David H. Koch Professor of Science at MIT, the director of the MIT Center for Precision Cancer Medicine, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the new study. “This could reveal new druggable targets or novel combination therapies.”

The study, published in Nature, is the product of a long-standing collaboration with senior authors Lewis Cantley at Harvard Medical School and Dana-Farber Cancer Institute, Benjamin Turk at Yale School of Medicine, and Jared Johnson at Weill Cornell Medical College.

The paper’s lead authors are Tomer Yaron-Barir at Columbia University Irving Medical Center, and MIT’s Brian Joughin, with contributions from Kontstantin Krismer, Mina Takegami, and Pau Creixell.

Kinase kingdom

Human cells are governed by a network of diverse protein kinases that alter the properties of other proteins by adding or removing chemical compounds called phosphate groups. Phosphate groups are small but powerful: When attached to proteins, they can turn proteins on or off, or even dramatically change their function. Identifying which of the almost 400 human kinases phosphorylate a specific protein at a particular site on the protein was traditionally a lengthy, laborious process.

Beginning in the mid 1990s, the Cantley laboratory developed a method using a library of small peptides to identify the optimal amino acid sequence — called a motif, similar to a scannable barcode — that a kinase targets on its substrate proteins for the addition of a phosphate group. Over the ensuing years, Yaffe, Turk, and Johnson, all of whom spent time as postdocs in the Cantley lab, made seminal advancements in the technique, increasing its throughput, accuracy, and utility.

Johnson led a massive experimental effort exposing batches of kinases to these peptide libraries and observed which kinases phosphorylated which subsets of peptides. In a corresponding Nature paper published in January 2023, the team mapped more than 300 serine/threonine kinases, the other main type of protein kinase, to their motifs. In the current paper, they complete the human “kinome” by successfully mapping 93 tyrosine kinases to their corresponding motifs.

Next, by creating and using advanced computational tools, Yaron-Barir, Krismer, Joughin, Takegami, and Yaffe tested whether the results were predictive of real proteins, and whether the results might reveal unknown signaling events in normal and cancer cells. By analyzing phosphoproteomic data from mass spectrometry to reveal phosphorylation patterns in cells, their atlas accurately predicted tyrosine kinase activity in previously studied cell signaling pathways.

For example, using recently published phosphoproteomic data of human lung cancer cells treated with two targeted drugs, the atlas identified that treatment with erlotinib, a known inhibitor of the protein EGFR, downregulated sites matching a motif for EGFR. Treatment with afatinib, a known HER2 inhibitor, downregulated sites matching the HER2 motif. Unexpectedly, afatinib treatment also upregulated the motif for the tyrosine kinase MET, a finding that helps explain patient data linking MET activity to afatinib drug resistance.

Actionable results

There are two key ways researchers can use the new atlas. First, for a protein of interest that is being phosphorylated, the atlas can be used to narrow down hundreds of kinases to a short list of candidates likely to be involved. “The predictions that come from using this will still need to be validated experimentally, but it’s a huge step forward in making clear predictions that can be tested,” says Yaffe.

Second, the atlas makes phosphoproteomic data more useful and actionable. In the past, researchers might gather phosphoproteomic data from a tissue sample, but it was difficult to know what that data was saying or how to best use it to guide next steps in research. Now, that data can be used to predict which kinases are upregulated or downregulated and therefore which cellular signaling pathways are active or not.

“We now have a new tool now to interpret those large datasets, a Rosetta Stone for phosphoproteomics,” says Yaffe. “It is going to be particularly helpful for turning this type of disease data into actionable items.”

In the context of cancer, phosophoproteomic data from a patient’s tumor biopsy could be used to help doctors quickly identify which kinases and cell signaling pathways are involved in cancer expansion or drug resistance, then use that knowledge to target those pathways with appropriate drug therapy or combination therapy.

Yaffe’s lab and their colleagues at the National Institutes of Health are now using the atlas to seek out new insights into difficult cancers, including appendiceal cancer and neuroendocrine tumors. While many cancers have been shown to have a strong genetic component, such as the genes BRCA1 and BRCA2 in breast cancer, other cancers are not associated with any known genetic cause. “We’re using this atlas to interrogate these tumors that don’t seem to have a clear genetic driver to see if we can identify kinases that are driving cancer progression,” he says.

Biological insights

In addition to completing the human kinase atlas, the team made two biological discoveries in their recent study. First, they identified three main classes of phosphorylation motifs, or barcodes, for tyrosine kinases. The first class is motifs that map to multiple kinases, suggesting that numerous signaling pathways converge to phosphorylate a protein boasting that motif. The second class is motifs with a one-to-one match between motif and kinase, in which only a specific kinase will activate a protein with that motif. This came as a partial surprise, as tyrosine kinases have been thought to have minimal specificity by some in the field.

The final class includes motifs for which there is no clear match to one of the 78 classical tyrosine kinases. This class includes motifs that match to 15 atypical tyrosine kinases known to also phosphorylate serine or threonine residues. “This means that there’s a subset of kinases that we didn’t recognize that are actually playing an important role,” says Yaffe. It also indicates there may be other mechanisms besides motifs alone that affect how a kinase interacts with a protein.

The team also discovered that tyrosine kinase motifs are tightly conserved between humans and the worm species C. elegans, despite the species being separated by more than 600 million years of evolution. In other words, a worm kinase and its human homologue are phosphorylating essentially the same motif. That sequence preservation suggests that tyrosine kinases are highly critical to signaling pathways in all multicellular organisms, and any small change would be harmful to an organism.

The research was funded by the Charles and Marjorie Holloway Foundation, the MIT Center for Precision Cancer Medicine, the Koch Institute Frontier Research Program via L. Scott Ritterbush, the Leukemia and Lymphoma Society, the National Institutes of Health, Cancer Research UK, the Brain Tumour Charity, and the Koch Institute Support (core) grant from the National Cancer Institute.

[tracychamberlainhigginbotham]

(via Thursday Thoughts: The gift of an eyebrow)

[ai-news]

Author(s): Dr. Mandar Karhade, MD. PhD. Originally published on Towards AI. HealthCare Generative AI and Production Hiccups — welcome! Artificial intelligence (AI) has woven its way into the fabric of healthcare over the past few decades, evolving f #AI #ML #Automation

[spotlightstory]

More than 50 research papers published by the Dana-Farber Cancer Institute (DFCI), a prestigious teaching center affiliated with Harvard Medical School, are under review this week following online claims that their images and data had been manipulated.

Sholto David, a British molecular biologist and blogger, wrote a post for the independent research integrity blog For Better Science on January 2, in which he accuses researchers at the institute of “data forgery.” The long and at times scathing blog post featured images such as protein bands, data plots and PCR results from the papers, which David alleges were manipulated via copy and paste or Photoshop. The studies in question had been published between 1999 and 2017.

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Top Harvard Cancer Institute Will Retract Six Studies and Correct 31 More After Photoshop Claims

Smithsonian Magazine By Christian Thorsberg January 24, 2024 More than 50 research papers published by the Dana-Farber Cancer Institute (DFCI), a prestigious teaching center affiliated with Harvard Medical School, are under review this week following online claims that their images and data had been manipulated. Sholto David, a British molecular biologist and blogger, wrote a post for the…

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Jonathan Byrnes, MIT Center for Transportation and Logistics senior lecturer and visionary in supply chain management, dies at 75

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Jonathan Byrnes, MIT Center for Transportation and Logistics senior lecturer and visionary in supply chain management, dies at 75

Jonathan L.S. Byrnes, a distinguished senior lecturer at the MIT Center for Transportation and Logistics (CTL), passed away peacefully on May 7 after a long battle with cancer, leaving behind a legacy of profound contributions to supply chain education, industry, and the MIT community. He was 75 years old.

“Jonathan was not just a brilliant mind in supply chain management,” reflects Yossi Sheffi, director of CTL and the Elisha Gray II Professor of Engineering Systems. “He was a cherished colleague who had been a part of CTL for over half its existence. His impact on our community and the field of logistics is immense.”

Byrnes dedicated over three decades to teaching and shaping the future leaders of supply chain management (SCM). He authored over 200 influential publications and guided thesis work for numerous students and researchers. In 2021, Byrnes endowed the Jonathan Byrnes Prizes for Academic Distinction and Leadership, awarded each spring by CTL to a residential and a blended SCM master’s student who demonstrate, in Byrnes’s own words, “both a strong academic record (but not necessarily the strongest), linked with a strong contribution to student life.”

Byrnes made a positive impact on countless MIT students. In 2019, to celebrate the 20th anniversary of the Master of Engineering in Logistics (MLOG)/SCM Program, several hundred alumni were asked to identify their most memorable class. Byrnes’s course, 1.261J – ESD.261J – 15.771J (Case Studies in Logistics and Supply Chain Management), was most frequently cited. Other anecdotal accounts and alumni surveys perennially note the course as their favorite and most highly recommended for its impact and influence on students’ careers.

Byrnes fostered a collaborative and discussion-oriented learning environment — a highly valued and sought-after experience of on-campus learning. “He was a gentle man, but was always so vigorous and energetic in class,” remembers Austin Saragih, MIT PhD student in transportation and a graduate research assistant at the MIT Megacity Logistics Lab, and a 2021 Byrnes Prize recipient.

Byrnes’s passion and influence extended beyond the realm of academia. He served on the boards of several companies, leaving an indelible mark on industry practices, and he co-founded Profit Isle Inc., revolutionizing profit analytics and acceleration.

Born in Lexington, Massachusetts, Byrnes earned his MBA from Columbia University in 1974 and his doctorate in business administration from Harvard University in 1980, where he served as president of the Harvard Alumni Association.

He is survived by his wife, Marsha (Feinman) Byrnes; sons Dan and Steve; daughter-in-law Nicole Ledoux; grandchildren Edison, George, and Adrian; and sister Pamela Byrnes and her husband Rick Jacobsen. He is predeceased by his daughter-in-law, Kristin Szatkiewicz Byrnes.

Remembrances may be made to Dana-Farber Cancer Center in gratitude to oncologist Toni Choueiri, or to the Experimental Model of Human Sarcoma Fund.