Category Archives: Gene Medicine

The Broad Foundation brings together stem cell scientists, engineers and physicians at USC and beyond

Developing new stem cell therapies requires more than a solo biologist having a eureka moment alone in the lab. Real progress relies on collaborations between biologists, engineers and physicians. Thats why The Eli and Edythe Broad Foundation has continued its support of two strategic initiatives: innovation awards bringing together teams of engineers and scientists from USC and Caltech, and clinical research fellowships for physician-scientists.

Engineering new approaches: The Broad Innovation Awards

For the fifth consecutive year, the Broad Innovation Awards are providing critical funding to USC-affiliated faculty members pursuing multi-investigator research collaborations related to stem cells. For the first year, these collaborations are also drawing on the expertise of biomedical engineers from Caltech. Each award provides $200,000 of funding for a one-year project.

Were very excited to be joining our colleagues at USC in pioneering new approaches to advancing stem cell research, said Stephen L. Mayo, chair of the Division of Biology and Biological Engineering at Caltech. Were thankful to The Broad Foundation for supporting cross-town collaborations between scientists with different expertise but common goals.

With support from a Broad Innovation Award, Andy McMahon, the director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, is collaborating with Caltech biomedical engineer Long Cai to leverage a new technology for understanding chronic kidney disease. The technology, called seqFISH, provides information about genetic activity taking place in intact tissueenabling the study of the interactions between cells in their native environments.

Dr. Cais seqFISH technology will provide an unprecedented insight into the cellular interplay underlying chronic kidney disease caused by a maladaptive response to acute kidney injury, said McMahon, who is the W.M. Keck Provost and University Professor of Stem Cell Biology and Regenerative Medicine, and Biological Sciences, as well as the chair of the Department of Stem Cell Biology and Regenerative Medicine at USC. We aim to better understand this maladaptive responsewhich is more common in malesin order to find new targets for preventing the progression to chronic kidney disease.

A second Broad Innovation Award brings together USC Stem Cell scientist Rong Lu and Caltech synthetic biologist Michael Elowitz. Their team will study the spatial organization of blood-forming stem and progenitor cells, also called hematopoietic stem and progenitor cells (HSPCs), which reside in the bone marrow. By pinpointing the locations of specific HSPCs, the scientists may find clues to explain why certain HSPCs are so dominantreplenishing the majority of the bodys blood and immune cells after a disruption such as a bone marrow transplantation.

Spatial advantages may be the primary drivers of what we refer to as the clonal dominance of certain HSPCs, said Lu, a Richard N. Merkin Assistant Professor of Stem Cell Biology and Regenerative Medicine, Biomedical Engineering, Medicine, and Gerontology at USC. Understanding the spatial competition between HSPCs could help improve bone marrow transplantation and provide new insights into aging and the development of diseases such as leukemiawhich are associated with clonal dominance.

Elowitz added: Thanks to the Broad Innovation Award and this exciting collaboration with Rong Lu, we will be able to bring a new, synthetic biology approach to record cell histories and read them out in individual cells within their native spatial context, providing new insights into fundamental questions in blood stem cell development.

A third Broad Innovation Award brings together three collaborators at USC: Michael Bonaguidi, an assistant professor of stem cell biology and regenerative medicine, biomedical engineering, and gerontology; Robert Chow, a professor of physiology and neuroscience, and biomedical engineering; and Jonathan Russin, an assistant professor of neurological surgery and associate surgical director for the USC Neurorestoration Center. Their project focuses on finding new approaches to treating epilepsy by studying neural cells called astroglia. These cells perform a variety of key functions that support the health of neurons in the brain, and they may also play a role in modulating epileptic seizures.

Although adults dont tend to generate many new brain cells, humans do produce a limited number of new astroglia, said Bonaguidi. We will examine these newborn astroglia at the single-cell level to better understand their role in epileptic patients, and to lay the groundwork for identifying new treatments.

The doctors are in: The Broad Clinical Research Fellowships

The Broad Clinical Research Fellowships are also entering their fifth consecutive year. These fellowships support stem cell research by physician-scientists and residents who intend to practice medicine in California.

These fellowships provide a very special opportunity for our medical residents to engage deeply in laboratory research, as a complement to their extensive training in patient care, said Laura Mosqueda, Dean of the Keck School of Medicine of USC. This valuable research experience gives them a much more complete perspective on how to meet the challenges of finding the best possible treatments for their patients.

A USC resident physician in general surgery, Kemp Anderson will spend his fellowship studying necrotizing enterocolitis, a very serious intestinal infection that affects nearly 10 percent of premature infants. Specifically, he will explore how a molecule involved in cellular communication, called farnesoid X receptor, or FXR, might contribute to this disease.

If FXR plays a role in compromising intestinal barrier function in these premature infants, then altering the activity of FXR could potentially yield treatment modalities for necrotizing enterocolitis, avoiding the morbidity and mortality associated with surgical intervention, said Anderson, who is performing the research under the mentorship of Christopher Gayer and Mark Frey at Childrens Hospital Los Angeles (CHLA). Im deeply appreciative of the benefactors and the selection committee for awarding me the Broad Clinical Fellowship, as it is allowing me devoted time to focus on this important project, and to become a more well-rounded physician through this academic pursuit.

Brittany Rocque, a resident physician in general surgery, will use her fellowship to seek better ways to predict, detect and diagnose immune rejection in patients who have undergone liver transplantation. Nearly 60 percent of pediatric patients and at least 15 percent of adult patients reject their liver transplants, and this can currently only be confirmed through an invasive surgical biopsy. Rocque is utilizing the technology Imaging Mass Cytometry to identify and analyze the types of immune cells involved in rejection.

My project has the potential to provide a noninvasive option to assess rejection in transplanted patients, and to expand our understanding of immune rejection, said Rocque, who is being co-mentored by Juliet Emamaullee and Shahab Asgharzadeh at CHLA. Im greatly looking forward to applying my passion for transplantation surgery in the context of basic science, and enhancing my appreciation for the nuances of research, thanks to the Broad Clinical Research Fellowship.

A hematology-oncology fellow who will be transitioning to a junior faculty position at USC next year, Caitlin ONeill will study a condition known as clonal hematopoiesis or CH, a phenomenon common in the aging population. CH involves genetic mutations that cause the expansion of a particular population of blood cells without leukemia or related malignancies. CH increases risks for certain health conditions including heart disease.

During her Broad Clinical Research Fellowship, ONeill will look at one mutation seen in patients with CH: a mutation to the gene called Tet methylcytosine dioxygenase 2, or TET2. ONeill will explore if this mutation promotes blood clots, inflammation and heart disease.

The goal is to inform therapies to prevent heart disease and leukemic progression in aging patients with CH, said ONeill, who is working with co-mentors Casey OConnell and Rong Lu at USC. Im very happy to be working on this project, with support from the Broad Clinical Research Fellowship, during my transition to becoming a faculty member at USC.

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Broad Foundation brings together stem cell scientists, engineers and physicians at University of Southern - Mirage News

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Strategy uses particles to target gene in specific immune cells

Using dual-energy X-ray absorptiometry to identify fat (white) in the body, researchers at Washington University School of Medicine in St. Louis found excessive fat in a mouse that had consumed a high-fat diet for six weeks (left). The mouse on the right ate the same diet, but the researchers blocked the activity of a gene in specific immune cells, resulting in that mouse not becoming obese.

Disabling a gene in specific mouse cells, researchers at Washington University School of Medicine in St. Louis have prevented mice from becoming obese, even after the animals had been fed a high-fat diet.

The researchers blocked the activity of a gene in immune cells. Because these immune cells called macrophages are key inflammatory cells and because obesity is associated with chronic low-grade inflammation, the researchers believe that reducing inflammation may help regulate weight gain and obesity.

The study is published May 1 in The Journal of Clinical Investigation.

Weve developed a proof of concept here that you can regulate weight gain by modulating the activity of these inflammatory cells, said principal investigator Steven L. Teitelbaum, MD, the Wilma and Roswell Messing Professor of Pathology & Immunology. It might work in a number of ways, but we believe it may be possible to control obesity and the complications of obesity by better regulating inflammation.

When people are obese, they burn fewer calories than those who are not obese. The same is true for mice. But according to co-first author Wei Zou, MD, PhD, an assistant professor of pathology & immunology, the researchers found that obese mice maintained the same level of calorie burning as mice that were not obese after the research team deleted the ASXL2 gene in the macrophages of the obese mice and, in a second set of experiments, after they injected the animals with nanoparticles that interfere with the genes activity.

Despite high-fat diets, the treated animals burned 45% more calories than their obese littermates with a functioning gene in macrophages.

Exactly why this prevented obesity in the mice isnt clear. Co-first author Nidhi Rohatgi, PhD, an instructor in pathology, said it appears to involve getting white fat cells which store the fat that makes us obese to behave more like brown fat cells which help to burn stored fat. The strategy is a long way from becoming a therapy, but it has the potential to help obese people burn fat at rates similar to rates seen in lean people.

A large percentage of Americans now have fatty livers, and one reason is that their fat depots cannot take up the fat they eat, so it has to go someplace else, Teitelbaum said. These mice consumed high-fat diets, but they didnt get fatty livers. They dont get type 2 diabetes. It seems that limiting the inflammatory effects of their macrophages allows them to burn more fat, which keeps them leaner and healthier.

Zou W, et al. Myeloid-specific Axsl2 deletion limits diet-induced obesity by regulating energy expenditure. The Journal of Clinical Investigation, May 1, 2020.

This work was supported by the National Heart, Lung and Blood Institute; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute of Allergy and Infectious Diseases and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH). Grant numbers HL1388163, AR064755, AR068972, AR070975, HL38180, DK56260, P30 DK52574, P41 EB025815, HL073646, DK102691, AI019653, DK109668, DK056341, AR046523, DK111389 and P30 AR074992. Additional funding from the Physician-Scientist Training Program at Washington University School of Medicine and the Childrens Discovery Institute.

Washington University School of Medicines 1,500 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, ranking among the top 10 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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Obesity prevented in mice treated with gene-disabling nanoparticles - Washington University School of Medicine in St. Louis

Val Sheffield, the Roy J. Carver Chair in Molecular Genetics at the University of Iowa Roy J. and Lucille A. Carver College of Medicine, has been elected tothe 2020 class of the American Academy of Arts andSciences.

Sheffield was recognized for playing a key role in constructing human genetic maps and developing efficient disease-gene discovery approaches. This paved the way for the completion of the human genome project and significantly contributed to genetic discoveries in blinding eye diseases, obesity, hypertension, and neurological disorders, potentially leading to noveltherapies.

The American Academy of Arts and Sciences, founded in 1780 by John Adams and John Hancock, is both an honorary society that recognizes and celebrates the excellence of its members and an independent research center convening leaders from across disciplines, professions, and perspectives to address significant challenges. Elected members join with other experts in cross-disciplinary efforts to produce reflective, independent, and pragmatic studies that inform public policy and advance the publicgood.

This year, 276 new members were elected and include notable scientists, artists, scholars, and leaders in the public, nonprofit, and private sectors. Sheffield joins 58 other leaders in the medical sciences specialty. Academy members are nominated and elected by current members and chosen for excellence in their field and a record of continuedaccomplishment.

Sheffield is eager to contribute hisexpertise.

Genetic and genomic data are increasingly being integrated into the practice of medicine. With my expertise in human molecular and clinical genetics and genomics, Im hoping to be a useful resource to the academy, Sheffieldsays.

This is an incredible honor and well-deserved national recognition. We are extremely proud of Dr. Sheffield and his achievements, says Brooks Jackson, UI vice president for medical affairs and the Tyrone D. Artz Dean of the Carver College of Medicine.Given these turbulent times, it is especially gratifying to be able to celebrate hissuccess.

Sheffield joined the UI in in 1990 to perform research and practice clinical genetics in the Division of Medical Genetics for the UI Stead Family Department of Pediatrics. He has spent his entire career at Iowa, where he served as director of the Division of Medical Genetics for 22 years until stepping down in January 2020. He conducts scientific research related to human genetic diseases, however, he has recently converted a portion of his lab to join researchers across the world fighting the coronaviruspandemic.

Since the COVID-19 shutdown, I have switched some of my laboratory personnel to a COVID-19 project. We are trying to devise a simple method for collecting samples from patients for COVID-19 testing that doesnt require nasal swabs (in short supply) or use medical personnel to collect samples. The person being tested will self-collect the sample, thus saving on personnel and personal protective equipment. I am hoping to get FDA approval soon for this method so that it can be used to expand needed testing throughout Iowa, Sheffieldsays.

At the UI, Sheffield trains doctoral and medical students as a professor of pediatrics and a professor of ophthalmology and visual sciences. He also is an investigator for the UI Institute for Vision Research and practices medicine, caring for patients with human genetic disorders. He has co-authored more than 330 peer-reviewed scientific papers. He previously was an investigator for the Howard Hughes Medical Institute (HHMI), from 1998 to2016.

The members of the class of 2020 have excelled in laboratories and lecture halls, they have amazed on concert stages and in surgical suites, and they have led in board rooms and courtrooms, says academy President David W. Oxtoby. These new members are united by a place in history and by an opportunity to shape the future through the academys work to advance the publicgood.

Sheffield attended Brigham Young University, where he earned a bachelors degree in zoology and a masters degree in developmental biology. He received a doctoral degree in developmental biology and a medical degreewith honors from the University of Chicago. He was a resident in pediatrics and fellow in medical genetics at the University of California, SanFrancisco.

His research has been funded by the National Institutes of Health (NIH) for 29 consecutive years, as well as by the Roy J. Carver Charitable Trust. Sheffields honors include the E. Mead-Johnson Award for Pediatric Research and the Lewis Rudin Prize from the New York Academy of Science, and he is a member of the National Academy of Medicine. Sheffield is board certified by the American Board of Medical Genetics and Genomics in both clinical genetics and clinical moleculargenetics.

Sheffield joins the following UI faculty and administrators who havebeen elected members of the American Academy of Arts andSciences:

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Val Sheffield elected to the American Academy of Arts and Sciences - Iowa Now

We partner with clients in life sciences and medical technology hubs around the world who are developing medical devices and diagnostic tools enabled by optics.

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Many of our clients turn to Optikos for additional engineering bandwidth or foraccess to the skills and experience their staff may not haveto develop an optically-based product or solution. When you need aflexible and scalable resource for engineering and assembly, we can work with you to quickly provide a powerful team during the most intense portions of a product development effort. We can then readily scale the team up or down according to the needs of the project.

Optikos clients are located worldwide, and our headquarters is in the greater Boston, MA area among the worlds top private- and public-sector healthcare innovators.The diverse nature of our clients and their applications requires our engineers to have the ability to adapt to the culture of an organization as well as to local and regional customs and regulations. Our teams have worked at the forefront of surgical and medical technologies, developing complicated designs that incorporate optics and photonics, opto-mechanics, software, electronics, and automation; and meet rigorous regulatory requirements, and we bring this experience to every new project we take on, no matter how large or small.

And when you transition to manufacturing, Optikos is well-positioned to help. Optikos leverages its world-renowned expertise in lens/sensor metrology and testing to ensure the performance and quality of what we design and manufacture. Well provide pilot production, test procedures, assembly instructions, and training to get you up and running quickly; well act on your behalf in identifying a manufacturer equipped to meet your needs; or well offer contract manufacturing at our facility. We do whatever is in our clients best interest.

Were ready to assist you in bringing new devices to market, including navigating strict regulations, clinical trials, and technological challenges associated with product prototype and production manufacturing. For more information, visit us online at optikos.com or reach out to us at sales@optikos.com.

Sponsored content by Optikos

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Optics makes amazing things possible in biological research and medicineand Optikos makes it happen - Mass Device

CAMBRIDGE, Mass., April 29, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, will report first quarter 2020 financial results after the Nasdaq Global Market closes on Wednesday, May 6, 2020. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its first quarter 2020 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 2553748. Please specify to the operator that you would like to join the "Sarepta First Quarter 2020 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta's website at http://www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics to Announce First Quarter 2020 Financial Results and Recent Corporate Developments on May 6, 2020 - GlobeNewswire

The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non-animal approaches to health hazard assessment for ethical and practical reasons. Although non-animal approaches are becoming increasingly popular, there are almost no studies of side-by-side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air-liquid interface (ALI) cultures of donor-derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems. 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non-Animal Methods for...