Randal Kaufman Archives - Sanford Burnham Prebys

Tag: Randal Kaufman

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Randal J. Kaufman among the world’s most influential scientists

AuthorSusan Gammon
Date

November 15, 2023

Randal J. Kaufman, PhD

Over the last decade, the publications of Randal J. Kaufman are among the top 1% in the world by number of citations

Sanford Burnham Prebys professor Randal J. Kaufman, PhD was included on Clarivate’s 2023 Highly Cited Researchers list, a global ranking of influential researchers based on the number of times their work has been cited in peer-reviewed publication over the last decade. Launched in 2014 by Clarivate, a global research analytics company, the list identifies scientists who have demonstrated exceptional influence in their respective fields.

“The Highly Cited Researchers list identifies and celebrates exceptional individual researchers at Sanford Burnham Prebys who are having a significant impact on the research community as evidenced by the rate at which their work is being cited by their peers,” says David Pendlebury, head of Research Analysis at the Institute for Scientific Information at Clarivate. “These individuals are helping to transform human ingenuity into our world’s greatest breakthroughs – and it is an honor to celebrate their achievements.”

The 2023 list includes 7,125 individuals from 67 countries. With 2,669 American researchers named to the list, the United States had the greatest number of highly cited researchers compared to any other country, representing 37.5 percent of the complete list.

Randal J. Kaufman, PhD  – Discovering how proteins fold

Randal J Kaufman has a legacy of scientific contribution that extends across academia and industry alike. His landmark studies in the 1980’s contributed to the discovery of the unfolded protein response, a ubiquitous cellular stress response that occurs when misfolded proteins accumulate in cells. This response has been associated with an enormous array of human disease, including cancer, neurological, metabolic, genetic and inflammatory disorders, as well as the symptoms associated with aging. Today, his work continues to focus on explaining how and why misfolded proteins contribute to cell malfunctions and death, and his findings continue to shape the research of others through his highly cited publications.

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Randal Kaufman included in $12 million initiative to improve hemophilia treatment

AuthorMiles Martin
Date

March 8, 2022

Randal J. Kaufman, PhD

The new project will help researchers better understanding why current gene therapy treatments aren’t working.

A multi-institute research collaboration including Sanford Burnham Prebys has just received a $12 million grant from the National Heart, Lung, and Blood Institute to improve hemophilia therapy. The award will fund three projects that could lead to safer and potentially curative treatments for the disorder. One of these projects will be led by Randal J. Kaufman, PhD, who directs the Degenerative Diseases Program at Sanford Burnham Prebys.

How viruses could be help treat hemophilia
Hemophilia is an X-linked genetic condition that prevents the blood from clotting properly. It occurs in about one out of 5,000 male births. In patients with severe forms of the disease, internal or external bleeding can be life threatening. Standard treatments for severe hemophilia involve intravenously replacing the clotting proteins that patients are unable to produce adequately on their own. However, a gene therapy approach uses viruses as a delivery mechanism to provide the body with the information it needs to start making its own clotting factors.

“Several companies have taken this forward into clinical trials, and in some of these trials, the patients initially looked like they were cured,” says principal investigator Roland W. Herzog, PhD, the Riley Children’s Foundation Professor of Immunology at Indiana University School of Medicine. “But what they all have in common is that they need to deliver a lot of the virus in order to get the desired results, and over time, clotting factor levels started to decline. So it’s clear that we need to further study the biology of this phenomenon.”

How this grant will help improve the process
In hemophilia A, which accounts for about 80% of all cases, patients do not produce enough of a clotting protein called factor VIII (FVIII). To better understand the mechanisms that are mitigating the effects of current drug candidates, Herzog is teaming up with some of the nation’s leading experts. 

Their program will focus on three major projects in gene therapy for hemophilia A:

  • Project 1 will focus on cellular toxicity and stress that can be induced by FVIII protein production. This project is led by Kaufman. 
  • Project 2 will focus on molecular virology and the development of viral vectors used in gene therapy to deliver the FVIII-encoding gene.This project is led by Indiana University School of Medicine professor of pediatrics Weidong Xiao, PhD
  • Project 3 will examine the immune system and its role in the interference of FVIII production over time. It is jointly led by Herzog and Ype P. de Jong, MD, PhD, assistant professor of medicine at Cornell University. 

Together, they hope to provide new insight that can lead to lower levels of toxicity and improved longevity of FVIII production in patients who are treated with gene therapy for hemophilia.

“This is an incredibly significant and urgent medical question, and it requires the synergy of multiple groups with different expertise to come together and solve a problem that they wouldn’t be able to solve on their own,” says Herzog. “My hope is that our studies will help the field as a whole move toward curing hemophilia A.”

The grant is titled “Toward Safer Gene Therapy for Hemophilia A” (P01HL160472). This post was adapted from a press release published by Indiana University School of Medicine.

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Scientists discover an early sign of type 2 diabetes: Misfolded proinsulin

AuthorMonica May
Date

March 19, 2020

Diabetic patient is using glucometer to check glucose level

The findings could lead to tests or treatments that help prevent type 2 diabetes.

Misfolded proinsulin—a protein the body normally processes into insulin—is an early sign of type 2 diabetes, according to a study by scientists at Sanford Burnham Prebys and the University of Michigan Medical School. The discovery, published in eLife, could lead to tests or treatments that help prevent people from developing type 2 diabetes.

“Understanding the molecular events that occur as prediabetes progresses to diabetes opens new avenues for us to detect or interrupt these processes,” says Randal Kaufman, PhD, director and professor in the Degenerative Diseases Program at Sanford Burnham Prebys and co-corresponding author of the study. “With this information, we can start to find interventions that might spare millions of people from a serious, lifelong condition.”

More than one in three Americans, or approximately 88 million people, have prediabetes—which is characterized by elevated blood sugar. If left untreated, within four years nearly 40% of people with prediabetes develop type 2 diabetes, which occurs when the body doesn’t use insulin properly. In 2017, the cost of treating diabetes exceeded $327 billion, according to the American Diabetes Association. Due to increasing obesity rates, the number of people with the condition—particularly children—is on the rise.

Identifying the molecular events that occur during progression from prediabetes to full-blown diabetes remains one of the most perplexing problems in diabetes research. In the study, the scientists set out to answer this question by tracking proinsulin folding in the beta cells of humans and mice that are healthy, prediabetic and diabetic.

These studies revealed that instead of undergoing its normal folding process, proinsulin proteins were abnormally linked to each other. Levels of the abnormal proinsulin accumulated as prediabetes progressed to type 2 diabetes. Obese mice in the earliest stages of diabetes had the highest levels of abnormal proinsulin in their beta cells.

“Proinsulin misfolding is the earliest known event that may contribute to the progression from prediabetes to diabetes,” says Kaufman. “Together, these studies show that abnormally linked proinsulin holds promise as a potential measure of how close someone may be to developing type 2 diabetes.”

Now, the researchers are set to uncover more details about this process, such as the proteins that interact with the misfolded proinsulin.

“Understanding the fundamental molecular events that lead to type 2 diabetes is critical as the number of people with prediabetes continues to rise,” says Kaufman. “If we don’t find preventive measures, we will soon have a diabetes epidemic.”

The study’s first author is Anoop Arunagiri, PhD; and the study’s senior author is Peter Arvan, both of the University of Michigan Medical School.

Additional authors include Leena Haataja and Fawnnie Pamenan of the University of Michigan Medical School; Ming Liu of the University of Michigan Medical School and Tianjin Medical University in China; Anita Pottekat and Pamela Itkin-Ansari of Sanford Burnham Prebys; Soohyun Kim of Konkuk University in South Korea; Lori M. Zeltser of Columbia University; Adrienne W. Paton and James C. Paton of the University of Adelaide in Australia; and Billy Tsai of the University of Michigan.

The study’s DOI is 10.7554/eLife.44532.

This work was supported by the National Institutes of Health (R01DK111174, R24DK110973 and R01DK48280) and the Juvenile Diabetes Research Foundation International (2-SRA-2018-539-A-B).

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Research points to new way to prevent optic nerve degeneration in glaucoma

AuthorJessica Moore
Date

June 2, 2016

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Over 3 million Americans have glaucoma, the group of eye diseases that damage the nerve that carries information from the eye to the brain. This damage slowly degrades patients’ vision, even with treatment. Current glaucoma drugs lower the pressure in the eye, which lessens the injury to the nerve, although it is not eliminated. Finding ways to protect the optic nerve could lead to treatments that are much more effective in preserving or restoring sight in glaucoma patients. Continue reading “Research points to new way to prevent optic nerve degeneration in glaucoma”

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Randal Kaufman among world’s most influential biologists

Authorkcusato
Date

February 4, 2016

dr. randal kaufman

Thomson Reuters has announced the world’s most influential scientific minds, and for the second time since 2014, Randal Kaufman, Ph. D., professor and director of SBP’s Degenerative Disease Program, is on that list. Thomson Reuters created the list based on scientists who write the most reports that rank among the top 1 percent cited by other scientists between the years 2003 and 2013. Analysts looked at more than 120,000 papers and recognized close to 3000 scientists.

Continue reading “Randal Kaufman among world’s most influential biologists”

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Antioxidant-rich diet could help stave off type 2 diabetes

AuthorGuest Blogger
Date

November 12, 2015

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Type 2 diabetes affects about 8% of all adults and is a leading cause of death worldwide. Despite its prevalence, relatively little is known about underlying molecular causes of the disease. SBP researchers now show that defects in a major cell stress pathway play a key role in the failure of pancreatic beta cells, leading to signs of diabetes in mice. The findings, published recently in PLOS Biology, also suggest that a diet rich in antioxidants could help to prevent or treat type 2 diabetes.

“The findings open new therapeutic options to preserve beta cell function and treat diabetes,” said senior study author Randal Kaufman, PhD, director of the Degenerative Diseases Program at SBP. “Because the same cell stress response is implicated in a broad range of diseases, our findings suggest that antioxidant treatment may be a promising therapeutic approach not only for metabolic disease, but also neurodegenerative diseases, inflammatory diseases, and cancer.”

Excess cell stress

Type 2 diabetes is caused by the failure of pancreatic beta cells to produce enough insulin—a hormone that helps to move a blood sugar called glucose into cells to be stored for energy. A major cause of type 2 diabetes is obesity, which can lead to abnormalities in insulin signaling and high blood glucose levels. Beta cells try to compensate by producing up to 10 times the usual amount of insulin, but this puts extra stress on a cell structure called the endoplasmic reticulum to properly fold, process, and secrete the hormone.

An increase in protein synthesis in beta cells also causes oxidative stress—a process that can lead to cell damage and death through the build-up of toxic molecules called reactive oxygen species. If the stress is too great, the beta cells will eventually fail. Approximately one-third of individuals with abnormal insulin signaling eventually develop beta cell failure and diabetes.

In the new study, Kaufman and his collaborators discovered that beta cell failure is caused by deficiency in a protein called IRE1α, which would otherwise help to protect cells against the stress of increased insulin production. Mice that lacked IRE1α in pancreatic beta cells did not produce enough insulin and developed high blood glucose levels, similar to patients with type 2 diabetes. IRE1α deficiency also caused inflammation and oxidative stress, which was the primary cause of beta cell failure. But treatment with antioxidants, which prevented the production of reactive oxygen species, significantly reduced metabolic abnormalities, inflammation and oxidative stress in these mice.

Taken together, the findings suggest that IRE1α evolved to expand the capacity of beta cells to produce insulin in response to increases in blood glucose levels. The study also implicates this major cell stress pathway in the development of type 2 diabetes and suggests that a diet rich in antioxidants could help to prevent or reduce the severity of the disease.

“Currently, we are testing the effects of antioxidants on glucose levels and beta cell function in mice,” Kaufman said. “If these studies prove successful, they could pave the way for clinical trials in humans and eventually lead to a new therapeutic approach for dealing with a major pandemic of the 21st century.”

This post was written by guest blogger Janelle Weaver, PhD

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Protecting pancreatic cells from stress could hold promise for treating diabetes

Authorsgammon
Date

April 21, 2015

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Type 2 diabetes is a chronic disease that affects about eight percent of adults worldwide, significantly increasing the risk of heart disease and stroke. This disease interferes with the body’s ability to make or use a hormone called insulin, which is produced by beta cells in the pancreas. These cells eventually fail in many patients with type 2 diabetes, making insulin replacement therapy a necessity for survival. However, this treatment is imprecise, onerous and often promotes weight gain, highlighting the strong need for better treatment options. Continue reading “Protecting pancreatic cells from stress could hold promise for treating diabetes”

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Dr. Randal Kaufman, one of the world’s most influential scientific minds

Authorsgammon
Date

July 18, 2014

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Last week, Thomson Reuters published a list of the world’s most influential scientific minds—195 of them in biology and biochemistry to be exact. Thomson Reuters created the list based on scientists that write the most reports that rank among the top 1 percent cited by other scientists between the years 2002 and 2012. To no surprise from us at Sanford–Burnham, Randal Kaufman, PhD, professor and director of the Degenerative Disease Program, was on the list.

Dr. Kaufman has been a major contributor to our understanding of how protein folding—and misfolding—lead to cell malfunctions and death. His research is particularly important to many diseases, including neurological, metabolic, genetic and inflammatory disorders. His research also explains some of the symptoms associated with aging.

Dr. Kaufman has a long history of contributions to science in industry and academia. As PhDgraduate student at Stanford University, he discovered that cancer cells develop drug resistance by gene amplification. As a post-doctoral fellow working with Nobel laureate Dr. Phillip Sharp at MIT, he studied gene amplification and new ways to express proteins in mammalian cells.

After post-doctoral work, Dr. Kaufman co-founded a company called the Genetics Institute Inc., a biotechnology company focused on treatments for hemophilia and many other disorders, including the development of technology that led to the FDA-approved drugs for hemophilia and erythropoietin for cancer and anemia.  After leaving the Genetics Institute, Inc. he took a position as HHMI investigator and endowed chair in the departments of Biological Chemistry and Internal Medicine at the University of Michigan.  He joined us at Sanford-Burnham in 2011 where he leads the Degenerative Disease Program.

Let us all take advantage of the fact that we have this incredible individual at our Institute and discover five interesting facts about the man with the brilliant brain.

If you could invite 5 people to dinner who would they be?Albert Einstein, Steve Jobs, Charles Darwin, Princess Diana and Brian Williams

What traits do  you most admire in people?Intelligence, confidence, and a sense of humor

What traits do you most deplore in people? Laziness, conceit and selfishness

What is your idea of a perfect weekend in San Diego? Sailing with my wife, Donna and three boys, Joshua, Kyle, and Maverick

If a genie granted you three wishes, what would they be? World peace, a cure for cancer, and unlimited NIH support for my research

From all of us at Sanford-Burnham, we congratulate you Dr. Kaufman and we hope your wishes come true!