Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.


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Apr 2, 2018 · Mayo scientists discover missing link in DNA damage repair

For years, researchers have known that our genome is protected by a system of detection, evaluation and repair processes that activate any time DNA damage occurs. Upon detection, the damage is assessed, repaired in one way or another, or, if it can’t be repaired the cell is cued to self-destruct. Much of that effort is set in motion by a signaling process involving the protein ubiquitin. Enzymes called ubiquitin ligases are charged with the task of tagging the damaged DNA with this ubiquitin protein to call in more help. What hasn’t been clear is how two of the key enzymes that mark the sites of DNA damage and amplify the repair response are called to action. Researchers theorized there was another actor involved, a missing link. Now Mayo Clinic researchers have discovered that link.

It’s L3MBTL2 – which stands for lethal-3 malignant brain tumor-like protein 2. It orchestrates the ubiquitin signaling resulting in the recruitment of the enzymes called RNF8 and RNF168 in a specific sequence. The Mayo findings were published in Nature Cell Biology.

Zhenkun Lou, Ph.D.

“To our knowledge, this is the first known report tying L3MBTL2 to DNA damage control,” says Zhenkun Lou, Ph.D., Mayo Clinic oncology researcher and senior author of the article. “Our finding also challenges the currently accepted theory that a histone, H1, is the primary link in this process.”

Significance of findings

Efficient repair of DNA strand breaks is the frontline in preventing mutations that could turn into cancer. Anything that interrupts that process or impedes programmed cell death could result in more damage or tumor development. The researchers emphasize that it’s important that this repair process be thoroughly understood in order to develop effective therapies to treat or prevent cancer. They further state that mutations in L3MBTL2 – when found in cancer patients – may damage or hinder the DNA repair process.

The research was supported by grants from the National Institutes of Health, including the National Cancer Institute, which funds the Mayo Clinic Cancer Center, and also by the Laura J. Siegel Breast Cancer Fellowship Award from the Foundation for Women’s Wellness.

In addition to Mayo Clinic scientists, the study included collaboration and coauthors from Jinan University, Guangzhou, China; The University of Minnesota Hormel Institute, Austin, Minnesota; and Tongji University School of Medicine, Shanghai, China.


Mar 6, 2018 · Minnesota Partnership awards five new research grants for collaborative projects

Epilepsy, Alzheimer’s disease, osteoporosis, colorectal cancer and bacterial infections are the targets of the research awards from the Minnesota Partnership for Biotechnology and Medical Genomics in 2018. This marks the partnership’s 15th year of spearheading new scientific ideas from Minnesota to improve health care for Minnesotans. The state-funded grants for these team science proposals total just under $5 million.

The five teams will initiate collaborative two-year projects that could transform the treatment of diseases that affect Minnesotans. All projects are selected on the basis of quality science, relevance of the medical need of the topic and potential of commercialization. Each team includes investigators from Mayo Clinic and the University of Minnesota. Projects must be truly collaborative ─ something that could not be pursued by either institution alone.

Read Mayo Clinic news release.


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Feb 10, 2017 · Mayo Clinic physician-researchers honored by national society

Two Mayo Clinic researchers have been named to the American Society for Clinical Investigation, bringing the total Mayo membership in the honorary society of physician-scientists to 39. Liewei Wang, M.D., Ph.D., a pharmacologist, and Martin Fernandez-Zapico, M.D., a pancreatic cancer biologist, were named to the society from several hundred nominees nationally. The society has 3,000 members.

Read the full news release on the Mayo Clinic News Network.

Learn about the American Society for Clinical Investigation.

Jan 9, 2017 · Single Allele Mutation Heightens Risk of Early-Onset Parkinson's

A collaboration of 32 researchers in seven countries, led by scientists at Mayo Clinic’s campus in Florida, found that a mutation in only one allele of a Parkinson’s gene, known as PINK1, increases the risk of early-onset disease. The finding, published recently in the journal Brain, addresses a longstanding debate about whether individuals need to inherit two copies of the mutation for an early form of the disease to occur.

Wolfdieter Springer, Ph.D.

Wolfdieter Springer, Ph.D.

The familial form of early-onset Parkinson’s, affecting patients as soon as age 45, is known to occur in individuals with mutations in both inherited alleles of the PINK1 (PTEN-induced putative kinase 1) gene. “This study showed that if a person inherits a specific mutation in just one PINK1 allele, the disease could develop at about age 55 or so. By contrast, the most common, nonfamilial forms of Parkinson’s develop at about age 65,” says the study’s senior investigator, Wolfdieter Springer, Ph.D., a neuroscientist at Mayo Clinic’s Florida campus.

Moreover, the study went on to explain how a single mutation in the PINK1 gene affects cells. PINK1 works with another gene, PARKIN, to clean up damaged mitochondria in the body’s cells. A specific mutation (p.G411S) in one allele of PINK1 substantially impairs this “quality control” pathway by causing a structural change in the enzyme that, in turn, inhibits those produced from other healthy PINK1 allele. “This rare mutation has an outsized effect, and the remaining levels of functional PINK1 protein are not enough to cope with damaged mitochondria,” Dr. Springer says. Without a clean-up mechanism, damaged mitochondria accumulate and become toxic, especially within neurons.

The study started with genetic findings when one of the lead authors, Andreas Puschmann, M.D., Ph.D., of the Department of Neurology, Skåne University Hospital, Sweden, was a visiting scientist at Mayo Clinic. Subsequent steps involved a “very effective synergetic” effort of clinical, structural and cell biologists, along with geneticists and data from thousands of affected patients “It took a real international collaboration to solve this puzzle,” he says.

The findings will not only be helpful to patients who want to understand their risk of disease, but also in the potential development of treatment. Dr. Springer’s team is moving ahead to explore how to preserve the enzymes of the PINK1/PARKIN pathway despite the presence of a mutation. “What we’ve learned about the structure-function changes of the enzyme is now helping us pursue drug design that addresses details of the protein on an atomic level,” he says.

This article originally appeared on the Mayo Clinic News Network.


Nov 8, 2016 · Becoming a Biomedical Scientist

“I have to tell you that the sheer intellectual joy of finding out how life works is really cool.”         – the late Susan Lindquist, Ph.D., pioneering genetic scientist

This last line from Dr. Lindquist’s obituary in the Sunday New York Times struck me as a timeless statement of enthusiasm and dedication. Dr. Lindquist graduated from Illinois and Harvard and went on to explain how genetic mechanisms work behind such conditions as Parkinson’s and Alzheimer’s.

Just hours after reading the Times, I received the link to the new video about Mayo’s role in creating scientists like Dr. Lindquist. I was thinking of her words as I watched it.

I can assure you, the enthusiasm in this footage is not staged or acted. Everyone and everything is real, including the determination. My colleagues at the Mayo Clinic Graduate School of Biomedical Research have been trying to capture and convey all of this for some time now… I think they just succeeded.

Aug 3, 2016 · Mayo Clinic Takes Medical Research to Kilimanjaro

mount-kilimanjaro-tanzaniaThe core group of Mayo Clinic researchers that moved their lab to the base camp at Mount Everest to study heart disease and aging are at it again, this time in Africa. Along with a party of nearly 35, they will be climbing Mt. Kilimanjaro, obtaining scientific data from the climbers along the way.

Led by Mayo physiologist Bruce Johnson, Ph.D. and joined by Amine Issa, Ph.D., Courtney Wheatley, Ph.D., and Jan Stepanek, M.D., among others, the group will monitor climbers’ heart rates, oxygen saturation, movement, energy expenditure, skin temperature and the quality of their sleep. They’ll also conduct ultrasound scanning to determine differences in younger and older climbers as they react to the altitude.

“It’s about comparing heart and lung function in this natural laboratory,” says Dr. Issa, who was part of the group on Everest. “We want to check on limitations to their functioning and whether or not a vitamin B3 supplement can help them.”

That supplement is being tested as part of Mayo’s collaboration with Thorne Research, a pharmaceutical company, which is a major sponsor of the climb. The researchers want to determine if an analog of vitamin B3 will increase metabolism efficiency and something called NAD – nicotinamide adenine dinucleotide – in the climbers’ blood. If so, it should help them adapt to the rigors of altitude sickness, which is in itself an analog for heart and lung disease.

Mayo will have eight in its research group. Everest mountaineer Conrad Anker of equipment sponsor The North Face, will lead the climb. In addition to Thorne Research, there will be individuals from Philips with equipment and analysis, and Biovotion,– also major equipment providers, – members of documentary production company Seadog — and a team from Griffith University in Australia. Also along will be Linda Wortman, cancer survivor and Mayo Clinic lung surgery patient.

The climbers will arrive in Tanzania on August 4th and begin their ascent on the 7th, to return in ten days. When possible, climbers will be posting their progress on social media via #kiliclimb2016. Kiliminjaro, a range consisting of three dormant volcanoes, is the highest mountain in Africa.

Jun 7, 2016 · Mayo Talks Research at BIO Conference

The Minnesota Pavilion at BIO 2016

The Minnesota Pavilion at BIO 2016

From Taiwan to Texas, anyone who has anything to do with biosciences is here in San Francisco to hear speakers, attend education sessions, but mostly to network and make contacts for business and research. Mayo Clinic is here along with Destination Medical Center in Minnesota to talk about our research activities and make a major announcement later today. Mayo’s research centers are represented in the Minnesota Pavilion at the conference and by several of our scientists and leaders.

We are spreading the word about Mayo being the NIH’s pick for the national biobank . It was announced just before Memorial Day and not many people noticed. It means Mayo will be handling the biobank storage for the government’s Precision Medicine Initiative. Biobanking is essential for research in medical genomics and advancing the future of medicine in the United States. The award comes with a $142 million grant over five years to build and maintain the space and freezer systems to store 35 million samples representing over 1 million research participants. In the words of Mayo Clinic Biobank director Steve Thibodeau, “This is a big deal.”

May 31, 2016 · We’ll bet on Dr. Ansell anytime

AnsellOn May 17, 2016, the U.S. Food and Drug Administration granted accelerated approval to nivolumab (Opdivo®) for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation.

Nivolumab also received a breakthrough therapy designation for the treatment of relapsed or refractory cHL after failure of autologous HSCT and brentuximab vedotin. Nivolumab also has orphan drug status for the treatment of Hodgkin’s lymphoma under FDA’s accelerated approval program.

Much of the credit for these achievements is due to the work of Stephen Ansell, M.D., Ph.D. of Mayo Clinic. Dr. Ansell led a multi-institution phase I clinical trial of nivolumab which found the immune-boosting drug to be a highly effective therapy for Hodgkin’s lymphoma. The study, which appeared in the New England Journal of Medicine in December, 2014 demonstrated that the drug was safe and led to an 87 percent response rate in patients who had failed on other treatments.

At the time, Dr. Ansell noted, “Nivolumab is a very promising agent that is reasonably well-tolerated and can easily be combined with other agents in the future. He also predicted, “It won’t be long before this particular agent will be approved, and then we will see other studies exploring how to administer it most effectively.”

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