Conrad Prebys Center for Chemical Genomics Archives - Sanford Burnham Prebys
Institute News

Melanoma’s mysteries revealed at Sanford Burnham Prebys

AuthorGreg Calhoun
Date

March 26, 2024

Cancer Center open house welcomes San Diego community to learn the latest about melanoma research

The Institute’s NCI-designated Cancer Center hosted the open house on Wednesday, March 20. It provided an opportunity for community members to meet scientists who seek to better understand melanoma and use this knowledge to improve treatment and prevention.

The event was sponsored by the center’s Community Advisory Board, an eight-member committee that focuses on advocacy, education and community engagement, as well as providing Cancer Center leaders and members with the perspectives of patients, survivors and their loved ones.

Open house participants could select from a variety of activities. Two labs provided brief poster presentations.

Ze’ev Ronai, PhD, director of the Sanford Burnham Prebys Cancer Center and the Jeanne and Gary Herberger Leadership Chair in Cancer Research, and his team discussed several areas of research, including the dissection of microbiota commensals which support the immune system’s fight against melanoma, the studies undertaken to understand melanoma addiction to the metabolic enzyme GCDH, and the development of new drugs to target the molecular machine that translates genetic instructions into proteins, which are known to be hyperactive in cancer cells.

Linda Bradley, PhD, professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys, and her group detailed their work on improving the immune system response to viral infections and cancer, including a new potential immune checkpoint therapy and efforts to rejuvenate overstressed immune cells to enhance the effectiveness of immunotherapy.

Attendees also could take tours of two different research facilities. Many participants enjoyed an insider’s view into the field of cryo-electron microscopy (cryo-EM), a technology that garnered three key innovators the 2017 Nobel Prize in Chemistry. The Cryo-EM core facility enables scientists to create 3D images of the cell and all its constituent parts that are accurate to the tiniest detail as it is able to capture individual atoms. Images taken using cryo-EM can be organized sequentially to develop films that show in real time how the cell’s many actors interact, helping scientists map interactions between drugs identified at Sanford Burnham Prebys and their target proteins, thereby advancing novel modalities for the treatment of melanoma and other cancers.

The second tour brought community members to the Conrad Prebys Center for Chemical Genomics. The Prebys Center is the Institute’s comprehensive center for drug discovery and chemical biology. Visitors were able to see the center’s state-of-the-art robots that enable researchers to quickly test the potential effectiveness of hundreds of thousands of compounds to find new prospective treatments. Many scientists at Sanford Burnham Prebys partner with the Prebys Center to conduct drug discovery searches based on new research findings, including those studying melanoma and other cancers.

Many of the visitors had the opportunity to visit a melanoma research laboratory to learn about research projects in the Ronai lab and view melanoma cells as seen under the microscope.

Open House guests conversing in Chairmen's Hall

Following the tours, Ronai shared an overview of the Cancer Center and highlighted recent accomplishments. Attendees interacted with Gregory Daniels, MD, PhD, a medical oncologist and melanoma expert from University of California San Diego and Steven Silverstein, a melanoma survivor, former president of the Melanoma Research Foundation and a melanoma research advocate. The open house concluded with an opportunity for guests to speak with cancer scientists and featured speakers during the evening reception.

“We were honored to provide our valued guests with the opportunity to learn about the research conducted at our Cancer Center, including ongoing melanoma research,” says Ronai. “Our open houses, which focus on different unmet needs in cancer, allow us to welcome and engage with the San Diego community, to share our findings and be inspired by patients and their loved ones.”

Institute News

Presenting The Conrad Prebys Foundation fellows

AuthorMiles Martin
Date

May 15, 2023

Thanks to a generous grant from The Conrad Prebys Foundation, a diverse group of early-career researchers will gain hands-on experience in drug discovery and translational medicine.

A new educational program at Sanford Burnham Prebys has welcomed a diverse group of early-career scientists to learn how to transform research discoveries into treatments for human diseases. The program was made possible by a generous grant from The Conrad Prebys Foundation as part of its mission to increase the diversity of San Diego’s biomedical workforce.

“Our mission at The Conrad Prebys Foundation is to create an inclusive, equitable and dynamic future for all San Diegans,” says Grant Oliphant, CEO at The Conrad Prebys Foundation. “San Diego is one of the top areas in the country for biomedical research, and we’re pleased to partner with Sanford Burnham Prebys to help strengthen the pipeline of diverse talent in life sciences research.”

Graduate students and postdoctoral fellows selected for the program will complete projects at the Institute’s Conrad Prebys Center for Chemical Genomics (Prebys Center), the nation’s leading nonprofit drug discovery center. The Prebys Center specializes in finding new medicines for diseases with a substantial unmet medical need in order to develop better therapies. 

“Thank you to The Conrad Prebys Foundation. I am beyond grateful for their support,” says predoctoral Prebys fellow Michael Alcaraz, who will complete his project on the links between aging and brain disease with Professor Peter D. Adams, PhD, and Steven Olson, PhD, executive director of Medicinal Chemistry at the Prebys Center. 

To help fulfill the Foundation’s mission, Sanford Burnham Prebys students and postdocs from historically underrepresented groups were encouraged to apply for the new program.

“Promoting diversity in the biomedical workforce is a founding principle of our educational program,” says Alessandra Sacco, PhD, vice dean and associate dean of Student Affairs in the Graduate School of Biomedical Sciences at Sanford Burnham Prebys. Sacco will oversee the new program alongside Dean Guy Salvesen, PhD, and Professor Michael Jackson, PhD

“Working actively to train people from all backgrounds gives opportunities to people who may not otherwise have had them—and it also improves the quality of the research itself,” she adds.

“Translational research is one of the biggest priorities in biomedicine right now because it’s how we turn discoveries into actual medicines,” says Sacco. “This program gives students and postdocs an opportunity to build the skills they need for translational research jobs in academia or industry.”

The fellowship will culminate in a final symposium next spring, where the fellows will present their research to their peers and to the wider community. 

“I’m looking forward to gaining more experience and making my contribution to the translational science at the Prebys Center,” says predoctoral Prebys fellow Merve Demir, who will complete a structural biochemistry project with Assistant Professor Jianhua Zhao, PhD, and Eduard Sergienko, PhD, director of Assay Development at the Prebys Center. 

The full list of fellows includes:
 

Postdoctoral Fellows

– Karina Barbosa Guerra [Deshpande Lab, Ed Sergienko co-mentor]
“SGF29 as a novel therapeutic target in AML”
 
– Merve Demir [Zhao Lab, Ed Sergienko co-mentor]
“Structural studies of MtCK and GCDH enzyme drug targets”
 
– Jerry Tyler DeWitt [Haricharan Lab, TC Chung co-mentor]
“Investigating the unique molecular landscape of ER+ breast cancer in black women” 
 
– Alicia Llorente Lope [Emerling Lab, Ian Pass co-mentor]
“Exploring PI5P4Kγ as a novel molecular vulnerability of therapy-resistant breast cancer” 
 
– Van Giau Vo [Huang Lab, TC Chung co-mentor]
“Identifying enhancers of SNX27 to promote neuroprotective pathways in Alzheimer’s disease and Down Syndrome”
 
– Xiuqing Wei [Puri Lab, Anne Bang co-mentor]
“Selective targeting of a pathogenetic IL6-STAT3 feedforward loop activated during denervation and cancer cachexia”

 

Predoctoral Fellows

– Michael Alexander Alcaraz [Adams Lab, Steven Olson co-mentor]
“Activating the NAMPT-NAD+ axis in senescence to target age-associated disease”
 
– Shea Grenier Davis [Commisso Lab, Steven Olson co-mentor]
“Examining PIKfyve as a potential therapeutic target in pancreatic cancer” 
 
– Patrick Hagan [Cosford Lab, Ian Pass co-mentor]
“Discovery and development of novel ATG13 degrading compounds that inhibit autophagy and treat non-small-cell lung cancer”
 
– Texia Loh [Wang Lab, Ed Sergienko co-mentor]
“Investigating the role of HELLS in mediating resistance to PARP Inhibition in small-cell lung cancer”
 
– Michaela Lynott [Colas Lab, TC Chung co-mentor]
“Identification of small molecules inhibiting ATF7IP-SETDB1 interacting complex to improve cardiac reprogramming efficiency”
 
– Tatiana Moreno [Kumsta Lab, Anne Bang co-mentor]
“Identifying TFEB/HLH-30 regulators to modulate autophagy in age-related diseases”
 
– Utkarsha Paithane [Bagchi Lab, TC Chung co-mentor]
“Identification of small-molecule enhancers of Honeybadger, a novel RAS/MAPK inhibitor” 
 

Institute News

Stepping into a scientist’s shoes at the Cancer Center Open House

AuthorMonica May
Date

June 20, 2019

Cancer research has led to new insights and novel medicines that have transformed the lives of parents, grandparents and children around the world. Yet cancer remains the number-one cause of death in San Diego (nationally, it is the second-leading cause of death). The quest for new and better treatments—and a world free of the disease—remains urgent. 

On June 13, 2019, the San Diego community—including many cancer survivors and their loved ones—had a unique opportunity to step into the shoes of a cancer researcher and see how cancer drugs are discovered at the open house of our NCI-designated Cancer Center. The facility is one of only seven National Cancer Institute (NCI)–designated basic research cancer centers in the nation. 

Following an introduction by Garth Powis, D. Phil., professor and director of the NCI-designated Cancer Center, guests embarked on guided lab tours. Attendees discovered how we’re working to find better ways to combat cancer, viewed highly specialized equipment—such as machines that model the low-oxygen environment surrounding a tumor—and donned lab coats to catch a glimpse of our ultra-high-throughput drug screening robot in action at our Prebys Center for Drug Discovery. The state-of-the-art technology at the Prebys Center can screen hundreds of thousands of potential drug candidates in one run, accelerating the time it takes to find new, promising compounds that may become tomorrow’s cancer treatments.

Guests also learned how San Diego, with a multitude of world-class research institutes, universities and biotech companies, is shaping the future of cancer diagnosis and treatment. And our Community Advisory Board, comprised of cancer research advocates and cancer survivors, were on hand to share the importance of factoring in patients’ perspectives as breakthrough science moves from “bed to bedside.”

See the science in action in these event photos.

Missed the event? We hope you can join us at our next open house in November. The event is free and open to the public. Check for more details at sbpdiscovery.org/calendar.

Many thanks to our Community Advisory Board (CAB), the host of the open house. Comprised of nine cancer research advocates, including many cancer survivors, this committee strives to create a dialogue between our scientists and the community. We are grateful for CAB’s efforts surrounding the event, which included helping our scientists prepare lay-friendly presentations and posters that were critical to the event’s success.

Interested in keeping up with our latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.

Institute News

Drug screen conducted at Sanford Burnham Prebys identifies new therapeutic avenues for Alzheimer’s disease

AuthorMonica May
Date

February 7, 2019

A screen of more than 1,600 Food and Drug Administration (FDA)–approved drugs performed at SBP’s Conrad Prebys Center for Chemical Genomics (Prebys Center) has revealed new therapeutic avenues that could lead to an Alzheimer’s disease treatment. 

The findings come from a collaboration between SBP scientists and researchers at the University of California San Diego School of Medicine, Leiden University Medical Center and Utrecht University in the Netherlands and were published in Cell Stem Cell

The hunt is on for an effective treatment for Alzheimer’s, a memory-robbing disease that is nearing epidemic proportions as the world’s population ages. Nearly six million people in the U.S. are living with Alzheimer’s disease. This number is projected to rise to 14 million by 2060, according to the Centers for Disease Control and Prevention (CDC). 

Scientists have known for many years that a protein called tau accumulates and creates tangles in the brain during Alzheimer’s disease. Additional research is revealing that altered cholesterol metabolism in the brain is associated with Alzheimer’s. But the relationship between these two clues is unknown. 

By testing a library of FDA-approved drugs against induced pluripotent stem cells (iPSC) neurons created from people with Alzheimer’s disease, the scientists were able to identify 42 compounds that reduced the level of phosphorylated tau, a form of tau that contributes to tangle formation. The researchers further refined this group to only include cholesterol-targeting compounds. 

A detailed study of these drugs showed that their effect on tau was mediated by their ability to lower cholesteryl esters, a storage product of excess cholesterol. These results led them to an enzyme called CYP46A1, which normally reduces cholesterol. Activation of this enzyme by the drug efavirenz (brand names Sustiva® and Stocrin®) reduced cholesterol esters and phosphorylated tau in these neurons, making it a promising therapeutic target for Alzheimer’s disease. Further mapping of the enzyme’s action(s) within a cell could reveal even more therapeutic targets. 

“Our Prebys Center is designed to be a comprehensive resource that allows basic research—whether conducted at SBP, academic and nonprofit research institutions or industry—to be translated into medicines for diseases that urgently need better treatments,” says study author Anne Bang, PhD, director of Cell Biology at the Conrad Prebys Center for Chemical Genomics at SBP. “We are proud that the Prebys Centers’ drug discovery technologies helped reveal new paths that could lead to a potential treatment for Alzheimer’s, one of the most devastating diseases of our time.” 
 


The senior author of the study is Lawrence S. B. Goldstein, PhD, distinguished professor at the University of California San Diego (UC San Diego) and scientific director of the Sanford Consortium for Regenerative Medicine. The co-first authors are Vanessa Langness, a PhD graduate student in Goldstein’s lab, and Rik van der Kant, PhD, a senior scientist at Vrije University in Amsterdam and former postdoctoral fellow in Goldstein’s lab. 

Additional study authors include Cheryl M. Herrera, Daniel Williams, Lauren K. Fong and Kevin D. Rynearson, UC San Diego; Yves Leestemaker, Huib Ovaa, Evelyne Steenvoorden and Martin Giera of Leiden University Medical Center; Jos F. Brouwers and J. Bernd Helms; Utrecht University; Steven L. Wagner, UC San Diego and Veterans Affairs San Diego Healthcare System.

Funding for this research came, in part, from the Alzheimer Netherlands Fellowship, ERC Marie Curie International Outgoing Fellowship, the National Institutes of Health (NIH) (5T32AG000216-24, IRF1AG048083-01) and the California Institute for Regenerative Medicine (RB5-07011).

Read more in UC San Diego’s press release. 
 

Interested in keeping up with Sanford Burnham Prebys’ latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.

Institute News

SBP and friends remember Conrad Prebys with a touching tribute

AuthorHelen I. Hwang
Date

October 11, 2017

With the brilliant sun descending over the famed Torrey Pines Golf Course overlooking the Pacific Ocean, a close knit of friends and loved ones gathered to pay tribute to Conrad Prebys and his lasting impact on Sanford Burnham Prebys Medical Discovery Institute (SBP). It might’ve been the same kind of gorgeous sunset that inspired Prebys to put down roots in California after moving from Indiana with $500 in his pocket.

T. Denny Sanford and Malin Burnham came to the podium and spoke about the loss of their dear friend Conrad. Burnham spoke about how much he admired Conrad’s “gut” feeling, which inspired him to become a loyal supporter to the Institute. In 2015, SBP was the recipient of Prebys’ extraordinary philanthropic gift of $100 million.

SBP President Kristiina Vuori, MD, PhD, recounted Conrad’s delightful visits and his longstanding relationship with the Institute. Michael Jackson, PhD, senior vice president of Drug Discovery and Development and head of the Conrad Prebys Center for Chemical Genomics, known as the Prebys Center, spoke highly about how impressed he was with Conrad’s intellectual curiosity and passion for science.

“Conrad’s generosity has enabled us to become a world-class facility, with the Prebys Center being recognized as one of the most comprehensive, nonprofit drug discovery centers in the world, conducting innovative drug discovery across all major disease areas – cancer, Alzheimer’s, Parkinson’s disease, heart failure, diabetes, autoimmune diseases, such as rheumatoid arthritis and Crohn’s disease,” said Dr. Jackson. In large part because of Conrad’s pivotal contribution, SBP is often chosen as a collaborative partner of choice among pharmaceutical companies, biotech companies, academic institutions and academic foundations all over the United States.

Debbie Turner also attended the tribute and enjoyed the walk down memory lane with Conrad and his relationship to SBP with a photo presentation of years past and a dedicated short video SBP produced celebrating Conrad’s life.

Guests enjoyed an outdoor buffet reception, while mingling with scientists who attended SBP’s Annual Symposium earlier that day. Nearly 300 scientists from all over the world gathered to attend SBP’s annual conference, which was themed “Frontiers in Single Cell Biology.”

After the touching tribute that brought a few of the guests to tears, friends gathered for a light reception of dessert and coffee and said their “goodbyes” until the next SBP event.

Our Annual Gala will be held on Saturday, October 14 at Coasterra on Harbor Island in downtown San Diego. Tickets are available here: SBP’s 2017 Annual Gala.  

 

Joan and Irwin Jacobs with Denny Sanford
Irwin and Joan Jacobs with Denny Sanford

 

Sheila and Jeffrey Lipinski with Debbie Turner
Sheila and Jeffrey Lipinsky with Debbie Turner

 

 

 

Institute News

Parkinson’s research benefits from powerful collaboration

AuthorDeborah Robison
Date

June 19, 2017

Medical discoveries may languish in laboratories for years without the necessary tools and means to drive findings further toward the development of novel therapeutics. This could have been the case for Dr. Pamela McLean, a Parkinson’s disease expert at the Mayo Clinic in Jacksonville, Fla., had a collaboration with SBP’s drug discovery team in Lake Nona not emerged.

McLean’s deep clinical experience and unique insights into the molecular basis of the disease, combined with SBP’s screening technology and drug discovery expertise, produced promising findings and attracted a significant grant from The Michael J. Fox Foundation (MJFF). Just recently, the researchers were awarded a special MJFF bridge grant to ensure that the science continues to move forward.

McLean studies the role of alpha-synuclein, a protein that misfolds and aggregates in the brain regions that are critically involved in Parkinson’s disease. She brought her cell-based models of alpha-synuclein protein “clumping” to SBP where the drug discovery team screened through 800,000 chemical compounds for substances that were capable of removing the abnormal protein and protecting the cells. Results from the initial study identified eight compounds as potential inhibitors of alpha-synuclein aggregation.

“Our current investigation will enhance the effectiveness of the drug candidates that we previously identified and advance them to pre-clinical development on the road to patient treatment,” said Dr. Layton Smith, director of SBP at Lake Nona Drug Discovery.

During this phase, chemistry teams will validate and refine the drug candidates’ biological activities. The process will likely eliminate some candidates in a testing funnel designed to narrow the compounds to those that exhibit the desired properties, such as inhibiting protein aggregation in the brain. Concurrently, McLean will explore the drug candidates’ mechanism of action to understand if the compounds work by blocking aggregation, enhancing removal of the clumps or by some other means. New therapies are critically needed to treat the more than 1 million Americans afflicted with Parkinson’s disease. Current medicines treat symptoms but do not reverse the effects of the disease.

Institute News

Existing compound holds promise for reducing Huntington’s disease progression

Authorsgammon
Date

December 7, 2015

Currently, there is no treatment to halt the progression of Huntington’s disease (HD), a fatal genetic disorder that slowly robs sufferers of their physical and mental abilities. In a new collaboration between SBP’s Conrad Prebys Center for Chemical Genomics (Prebys Center) and the University of California, San Diego School of Medicine, researchers have discovered that an existing compound, previously tested in humans for diabetes, offers hope for slowing HD and its symptoms. Continue reading “Existing compound holds promise for reducing Huntington’s disease progression”

Institute News

SBP Collaborates with NIH’s Translational Science Center on pancreatic cancer

Authorsgammon
Date

October 13, 2015

The National Center for Advancing Translational Sciences (NCATS) has initiated a novel collaborative study with Pamela Itkin-Ansari, PhD., to screen for drugs that reprogram pancreatic cancer cells back to a normal, non-threatening phenotype. The collaboration is based on Itkin-Ansari’s research and development of a screening platform to find drugs that induce the overexpression of E47, a protein that binds to specific DNA sequences, causing cells to differentiate to acinar cells—cells with normal pancreatic cell traits and characteristics.

Continue reading “SBP Collaborates with NIH’s Translational Science Center on pancreatic cancer”

Institute News

Pathway that controls cancer cell proliferation discovered

Authorsgammon
Date

August 13, 2015

In a new study by SBP, researchers have identified a novel kinase cascade that regulates mTORC1, a protein complex implicated in the control of cancer cell growth in response to nutrients. The study, published in Cell Reports, provides further insight into the control of mTORC1 activation, and highlights several new potential drug targets to treat human pathologies linked to mTORC1 deregulation. Continue reading “Pathway that controls cancer cell proliferation discovered”