Child malnutrition remains an alarming and appalling scourge.

In 2022, according to the World Health Organization, 148 million children in the world under 5 years were too short for their age (stunting) and another 45 million were too thin for their height (wasting) due to inadequate diet and nutrition.

Researchers around the world, including Andrei L. Osterman, PhD, professor in the Immunity and Pathogenesis Program at Sanford Burnham Prebys, have been investigating potential remedies, in particular some of the consequences of malnutrition, such as disturbed metabolism and immune/gut function.

In a new paper published October 2, 2024 in Science Translational Medicine, the multi-institutional team (including Osterman and colleagues at SBP) describe an interventional diet that essentially repairs the gut microbiome in children with moderate to severe acute malnutrition.

They conducted a three-month randomized controlled trial of a specialized food supplement in 12- to 18-month-old Bangladeshi children living in rural and urban slums with moderate acute malnutrition who had already been treated in hospital for severe acute malnutrition. The supplement, called microbiota-directed complementary food or MDCF-2, contains chickpea flour, peanut flour, soy flour, green banana, sugar, soybean oil and a vitamin-mineral premix, a formulation designed to promote the growth of therapeutic gut bacteria and improve the overall health and balance of the gut microbiome.

They found that MDCF-2 improved weight-for-age better than the traditional ready-to-use supplementary food (RUSF) used by relief agencies and others, which is composed of more traditional ingredients like rice, lentil, sugar, soybean oil and skimmed milk powder mixed with vitamins and minerals.

When excluding children unable to continue study participation due to severe flooding during the trial, the study authors also reported improvement of stunting at a faster rate. They tied these improvements in children’s health to Prevotella copri–associated metabolic changes.

P. copri (recently renamed as Segatella copri) is a bacterium found abundantly in the human gastrointestinal microbiome. Past studies have reported both positive and negative associations with health and disease. In the former, for example, healthy bacterial colonization of the gut has been positively correlated with conditions like inflammation, insulin resistance and diarrhea. It appears to be a major player in regulating dietary metabolism.

The bacterium is more common in non-Westernized populations consuming a diet rich in plants—the bacterium’s source of nutrients. In Western populations, it is associated with consumption of fruits and vegetables.

Genomic reconstruction of the metabolic potential of P. copri strains positively associated with infants’ health improvement confirmed their unique ability to utilize a large repertoire of plant-derived polysaccharides comprising MDCF-2 diet.

“This study can be viewed as a test of the generalizability of the efficacy and mechanism of action of MDCF-2 in acutely malnourished children,” said Osterman. “The main findings include the demonstration of significantly higher efficacy of MDCF-2 vs RUSF with respect to the improvement of (weight) growth.

“The success of the treatment was also manifest by beneficial changes in microbiome composition and by global changes of a range of serum protein biomarkers associated with healthy development.”

The findings, he said, also provide proof-of-concept that improving gut microbial health can be achieved using therapeutic nutrition and offers further guidance on how best to use microbiota-directed complementary foods.

Annual event shines spotlight on research conducted by postdoctoral associates and graduate students at Sanford Burnham Prebys.

“When I reflect on the most fun I’ve had during my career as a scientist, it was during my postdoctoral fellowship,” said Ye Zheng, PhD, Becky and Ralph S. O’Connor Chair and professor in the NOMIS Center for Immunobiology and Microbial Pathogenesis at the Salk Institute, during his keynote address at the 23^rd Annual Biomedical Research Symposium at Sanford Burnham Prebys on September 19, 2024.

“As a postdoc, every time I woke up, I would think about my scientific projects and then go to lab to work with interesting people and do exciting experiments. I had few, if any, distractions. It’s a unique opportunity, and I hope you treasure it.”

Zheng’s words of encouragement helped set the stage for a day filled with a variety of presentation formats to showcase the work of postdoctoral associates and graduate students at the institute. Peter D. Adams, PhD, director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, underscored the event’s importance in his opening remarks.

“This is how science works. You all convening and discussing your work today provides a platform for building new and innovative collaborations.

“You are the next generation of biomedical researchers, and there is no greater pleasure for me as a scientist than to see postdocs and students partnering with one another and enjoying working together.”

The symposium featured three scientific sessions with keynote presentations, podium lectures and brief “flash talks” in which speakers were limited to two minutes and a single slide to entice attendees to visit their posters. Participants voted in a science art competition and for best podium and flash talks.

Following the scientific sessions, Alicia Llorente Lope, PhD, a postdoctoral associate in the lab of Brooke Emerling, PhD, presented the 2024 Mentor of the Year Award to Alexandre Colas, PhD, the associate dean of admissions in the Graduate School of Biomedical Sciences and associate professor in the Development, Aging and Regeneration Program.

Linda Bradley, PhD, a professor in the Cancer Metabolism and Microenvironment Program and the faculty advisor for postdoctoral training, provided the symposium’s closing remarks. She reminded the audience that the symposium was planned for this week because it was National Postdoc Appreciation Week from September 16-20.

“I want to thank our postdocs for their incredible efforts driving the research forward in our labs,” she said. “I hope we can continue to enhance our environment and provide the best possible opportunities for training and mentorship here at the Institute.”

The 23^rd Annual Biomedical Research Symposium concluded with a poster session and happy hour reception. Postdoctoral associate and graduate school alumni were invited to these events to meet with current graduate students and postdoctoral associates and reconnect with their colleagues.

Symposium planning is coordinated by the Sanford Burnham Prebys Science Network, a group of postdoctoral associates and graduate students interested in professional development, networking and social events, and the institute’s Office of Education, Training and International Services.

“It was a terrific experience working together to build this year’s program,” said Valeria Guglielmi, PhD, a postdoctoral associate in the lab of Maximiliano D’Angelo, PhD, and member of the institute’s Science Network. “I’m especially grateful to our speakers, poster presenters and scientific artists for bringing excellent work that we could highlight.”

Additional awards given at the symposium included:

• Best podium talk – Judges’ selection
  Valeria Guglielmi, PhD
  Postdoctoral associate in the D’Angelo lab
• Best podium talk – Popular vote
  James Marchant, PhD
  Postdoctoral fellow in the Colas lab
• Best flash talk – Popular vote
  Theophilos Tzaridis, MD
  Postdoctoral fellow in the Adams lab
• Best poster – Judges’ selection
  Armin Aabish Gandhi, PhD
  Pstdoctoral associate in the Adams lab
• Best science art – Popular vote
  Carolina Cano Macip
  Graduate student in the Tian lab

Speakers at the symposium included:

Scientific Session I—moderated by Michaela Romero and Armin Aabish Gandhi, PhD

• Cheng-Ju Kuo, PhD
  Postdoctoral associate in the Kumsta lab
  “Temporal and spatial regulation of the autophagy-regulating transcription factor TFEB/HLH-30 in hormesis and aging”
• Ximena Diaz Olea
  Graduate student in the Ronai lab
  “Control of melanoma development by B. rodentium in germ free mice”
• Huijie Huang, PhD
  Postdoctoral associate in the Huang lab
  “SORLA upregulation suppresses global pathological effects in aged taupathy mouse brain”

Scientific Session II—moderated by Katya Marchetti, Namratha Nadig and Chiara Nicoletti, PhD

• Adarsh Rajesh
  Graduate student in the Adams lab, “A novel role of P21-CyclinD1-CDK6 complex in regulating interferon signaling in senescence and aging” 
• James Marchant, PhD
  Postdoctoral fellow in the Colas lab, “Single-construct cardiac programming gene therapy for heart failure”
• Valeria Guglielmi, PhD
  Postdoctoral associate in the D’Angelo lab
  “The nuclear pore complex component Nup358 regulates intestinal epithelium homeostasis”
• Theophilos Tzaridis, MD
  Postdoctoral fellow in the Adams lab, flash talk
• Evodie Koutouan
  Graduate student in the Pasquale lab, flash talk
• Sviatlana Zaretski
  Graduate student in the Adams lab, flash talk

Scientific Session III—moderated by Linda Chang and Theophilos Tzaridis, MD

• Gabriele Guarnaccia
  Graduate student in the Sacco lab
  “Serum amyloid protein A1 (SAA1) impairs myogenesis and myotube size in pancreatic cancer cachexia”
• Jessica Proulx, PhD
  Postdoctoral associate in the Adams lab
  “Investigating the role and therapeutic potential of HNF4α in loss of hepatocyte cell identity with age”
• Michaela Romero
  Graduate student in the Colas lab, flash talk
• Shanshan Yin, PhD
  Postdoctoral associate in the Adams lab, flash talk
• Guillem Lambies Barjau, PhD
  Postdoctoral associate in the Commisso lab, flash talk

In an essay, Michael R. Jackson, PhD, senior vice president for drug discovery and development at Sanford Burnham Prebys, explains.

Apart from the occasional moment of serendipity, the development of first-in-class drugs has always been more grind than grand, requiring as much as a decade and hundreds of millions of dollars to bring a new medicine to market. Most drug discovery efforts never reach that goal.

The more we learn about the molecular details of life — the previously unseen and unknown biology of different molecules and how they interact in health and disease — the more complex we realize it is, leaving much uncertainty as to what to target with a drug and how best to achieve desired results.

Indeed, the overall success rate of discovering new drugs, especially small molecules, has not dramatically improved over the past 20 years. While incremental advances have occurred, considerable risk and uncertainty remains in every step of the process.

Artificial intelligence (AI) and related advances are poised to change this reality, and rapidly. They are reshaping almost every stage of the drug discovery process, from identifying drug targets and simulating molecular interactions to designing drugs de novo (entirely from scratch) and accurately predicting which are most likely succeed before actual testing or clinical trials.

AI promises transformational progress in discovering drug. We can work faster, cheaper and more efficiently.

Perhaps the most impactful step to be improved is the selection of which molecule (typically a protein) to target with a drug. In a marriage of medical informatics and bioinformatics, data scientists are using AI to merge huge multi-omic datasets to reveal the mechanisms of disease, and which targets should be drugged. Downstream of this critical decision are three stages of drug development all of which seem destined to be revamped by AI:

First, for small molecule drugs we need to find a chemical that interacts with the selected drug target in a way that prevents, inhibits or erases a disease or its symptoms. Traditionally, this might entail screening 500,000 or more random chemicals in the hope that a few will bind (so called hits) that can be further developed into a drug.

Technologies like cryo-electron microscopy now allow us to visualize the three-dimensional structure of biomolecules alone or in complexes. We can see at the molecular level precisely how a chemical, found in a screen, fits into a protein target, not unlike a key into a lock or a jigsaw piece into a puzzle.

Exactly how a chemical binds informs on whether it inhibits, promotes or alters the function of the drug target. It can help medicinal chemists optimize the fit of the bound chemical.

With that information, emerging artificial intelligence tools can tap into and help make sense of vast, ever-growing databases, then suggest the most promising chemicals, which are similar to screening hits but can be calculated to fit the pocket better.

And in a huge step, AI- driven processes can be deployed to identify completely new binding chemicals that are chemically different from screening hits. This is achieved by a process called “in silico docking,” in which the fit of billions of different chemicals is calculated. A massively parallel computational effort is required to accomplish this scale of activity. It was not achievable until the advent of AI chips.

This is research driven by calculated hypothesis, not educated guesswork, and it happens in silico, meaning through computer modeling and simulation. It’s all virtual, compressing years of work into months, weeks or days. AI and machine learning processes have put this stage of the drug discovery process on steroids.

Second, drugs need to have other properties beyond simply binding to their target so that they can be taken as once-a-day pills, safe as well as efficacious. Recent advances in deep learning techniques allow the drug like properties of a chemical to be more accurately predicted by a computer. As this can be done very rapidly and before a chemical is made, it allows a medicinal chemist to focus on making only those compounds that have properties suitable to be a drug. While predicting drug properties is not new, AI has greatly enhanced predictive power, impacting the pace and success rates.

Third, human testing can be much more precise. Designed drugs can be refined to meet extremely specific medical needs. You have data to show which drug candidates are most likely to be effective for different types of patients and diseases and in combination with other drugs. As a result, clinical trials can be more focused, shorter and less costly. Remedies can get to patients who need them faster.

All of this happens universally. Most data is shared. Used effectively, AI informs everybody’s work, though human ingenuity and innovation remain critical. Scientists still need to interpret the data and make ensure that hypotheses are rigorously tested.

The future of drug discovery and development is simply bigger and better with AI. Researchers aren’t limited to what they’ve discovered or learned alone or in their labs. They now have tools to explore and exploit boundless troves of data and knowledge generated by the entire scientific enterprise.

Progress and achievement won’t come without bumps and glitches, of course. There are fundamental issues to address, such as access to the enormous computing powers and resources necessary to effectively use AI, new imaging technologies and other tools. Researchers, labs and institutions unable or unwilling to embrace these technologies may be left behind.

Going all in on AI isn’t just the smart choice. It’s the only choice.

---

Programming in a Petri Dish, an 8-part series

How artificial intelligence, machine learning and emerging computational technologies are changing biomedical research and the future of health care

• Part 1 – Using machines to personalize patient care. Artificial intelligence and other computational techniques are aiding scientists and physicians in their quest to prescribe or create treatments for individuals rather than populations.
• Part 2 – Objective omics. Although the hypothesis is a core concept in science, unbiased omics methods may reduce attachments to incorrect hypotheses that can reduce impartiality and slow progress.
• Part 3 – Coding clinic. Rapidly evolving computational tools may unlock vast archives of untapped clinical information—and help solve complex challenges confronting health care providers.
• Part 4 – Scripting their own futures. At Sanford Burnham Prebys Graduate School of Biomedical Sciences, students embrace computational methods to enhance their research careers.
• Part 5 – Dodging AI and computational biology dangers. Sanford Burnham Prebys scientists say that understanding the potential pitfalls of using AI and other computational tools to guide biomedical research helps maximize benefits while minimizing concerns.
• Part 6 – Mapping the human body to better treat disease. Scientists synthesize supersized sets of biological and clinical data to make discoveries and find promising treatments.
• Part 7 – Simulating science or science fiction? By harnessing artificial intelligence and modern computing, scientists are simulating more complex biological, clinical and public health phenomena to accelerate discovery.
• Part 8 – Acceleration by automation. Increases in the scale and pace of research and drug discovery are being made possible by robotic automation of time-consuming tasks that must be repeated with exhausting exactness.

Researchers reveal a step-by-step guide to constructing stitched-together protein complexes capable of recycling most of the proteins in our cells

Scientists at Sanford Burnham Prebys have developed a clearer picture of how crucial machinery in the human cell’s recycling process for obsolete and misshapen proteins—known as proteasomes—are formed.

“Proteasomes are absolutely essential for health,” said Jianhua Zhao, PhD, an assistant professor in the Cancer Metabolism and Microenvironment Program and senior author on the new study. “An estimated 80% of proteins within the cell are degraded by proteasomes to maintain a healthy balance as new proteins replace those that have fulfilled their function or became misfolded and potentially harmful.”

Issues with proteasomes can contribute to certain cancers and are associated with age-related diseases, so a better understanding of how these prodigious protein degraders are made may lead to new treatments for many conditions.

Zhao and his team published results on September 18, 2024, in Nature Communications, that provide new details about stages in the process of proteasome assembly that had eluded investigators. Within a long and detailed molecular dance including more steps of choreography than a K-pop music video, earlier research attempts focused on the middle phases in the process.

“We have now provided data on the earlier and later steps of how proteasomes are constructed in cells,” said Hanxiao Zhang, a graduate student at Sanford Burnham Prebys and first author on the study. “This is really difficult to do as the later stages feature complex enzymatic reactions at a rapid pace, while the earlier steps focus on smaller and less stable protein complexes.”

Zhang, Zhao and team investigated the fabrication of the canonical form of proteasome complexes found in humans, animals and plants. This proteasome, called the 20S proteasome, is marked by the coming together of four stacked rings comprised each of seven protein building blocks known as either alpha or beta subunits. The two rings of beta subunits at the center are sandwiched by two rings of alpha subunits.

The final 20S proteasome product looks less like cartoon mechanized lions forming a microscopic Voltron and more like a humble barrel, albeit just as destructive to proteins targeted for recycling. To see precisely how this barrel of proteins is joined, the researchers used gene editing techniques to tag helper proteins that bind with alpha and beta subunits and assist them in connecting to form their respective seven-piece rings.

To view the interactions between these marked faciliatory proteins—called chaperones—and the subunits as they link up into rings and stack in layers to form the 20S proteasome barrel, the scientists captured images using cryogenic electron microscopy (cryo-EM). This technology enables investigators to create 3D images of the cell and all its constituent parts that are accurate to the tiniest detail due to the ability to render 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.

The research team shed new light on how two protein chaperones bind on the top of the alpha subunit ring as it is constructed and are flanked by two chaperones on the bottom. With this initial ring taking the place of the metaphorical lid on what will become a barrel of four protein rings, the scientists also showed how the two bottom chaperones “under the lid” are removed and replaced by a different chaperone, and eventually by the rings of beta subunits that form the middle section of the 20S proteasome’s barrel shape.

“Learning more about the assembly of proteasomes may provide us with opportunities to leverage this knowledge to either target certain cancers or improve outcomes with aging,” said Zhao. “We also plan to use this data to make our own proteasomes in the laboratory and potentially design better proteasomes.”

Zhao believes that this may enable the findings to have wider implications beyond cancer and aging.

“What we’re looking at is not necessarily something that’s limited to humans,” added Zhao. “We’re also looking at host and pathogen interactions.”

This potential avenue led Zhao to collaborate with Anthony O’Donoghue, PhD, an associate professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego, to develop proteasome-based inhibitors to treat parasitic infections.

---

Additional authors on the study include Chenyu Zhou and Zarith Mohammad.

The study was supported by the National Institutes of Health (R35 GM147487 and S10 OD026926) and National Cancer Institute (Cancer Center Support Grant P30 CA030199).

Molecular graphics and analyses were performed with UCSFChimeraX, which is supported by the NIH (R01-GM129325) and the National Institute of Allergy and Infectious Diseases Office of Cyber Infrastructure and Computational Biology.

The study’s DOI is 10.1038/s41467-024-52513-0.

The four-day event included talks from experts from across North America and opportunities to discuss improving experimental methods and approaches to analyzing the resulting data.

Researchers convened at Sanford Burnham Prebys in La Jolla from September 12-15 to hear presentations from their peers and confer about the latest developments in modifying the genomes of mammalian animal models to advance biomedical research.

Anindya Bagchi, PhD, associate professor in the Institute’s Cancer Genome and Epigenetics Program, planned the 4^th Mammalian Genome Engineering Symposium, which included 26 presentations from experts across the United States and Canada. Attendees asked many questions throughout, and numerous speakers commented on how valuable the conversation at the meeting was for refining planned experiments and considering new ideas and approaches.

“It was a truly enjoyable and thought-provoking meeting,” said Angela Liou, MD, an instructor in the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys and pediatric oncologist and hematologist at Rady Children’s Hospital-San Diego. “It also was incredibly helpful in informing the next steps of my research project.”

“I’m so grateful for the invitation to attend this symposium,” said Praveen Raju, MD, PhD, the Nathan Gordon Chair in Neuro-Oncology and medical director of the Pediatric Neuro-Oncology Program at Rady Children’s Hospital-San Diego and director of the Pediatric Neuro-Oncology Program at the University of California San Diego School of Medicine.

“The presenters and attendees were welcoming and collaborative, and I certainly learned a lot.”

The symposium brings together the Mammalian Genome Engineering Group, which was formed by a small group of genome engineering enthusiasts including Bagchi, Nada Jabado, MD, PhD, professor of Pediatrics and Human Genetics at McGill University and a hematologist and oncologist at Montreal Children’s Hospital; David Largaespada, PhD, a professor of Pediatrics, Genetics, Cell Biology and Development at the University of Minnesota Medical School and the associate director for Basic Research in the Masonic Cancer Center; and Michael Taylor, MD, PhD, The Cyvia and Melvyn Wolff Chair of Pediatric Neuro-Oncology at Texas Children’s Cancer and Hematology Center and professor of Pediatrics (Hematology-Oncology) at Baylor College of Medicine.

The group is interested in developing functional models of genomic and epigenetic mutations associated with human diseases—especially cancers—that are difficult to recreate in animal models. The group’s first symposium was coordinated by Taylor in Napa, Calif., in 2014, followed by the 2^nd symposium that was organized by Jabado in Montreal in 2015. After a hiatus, the group was revived in 2023 with the 3^rd symposium hosted again by Taylor in Houston.

“We believe this symposium will, in the coming years, become a leading forum for discussing cutting-edge genomic and epigenomic approaches to tackle challenging genetic and epigenetic mutations,” said Bagchi. “These approaches are likely to become standard practice in the near future.”

The Sanford Burnham Prebys scientists that presented at the 4^th Mammalian Genome Engineering Symposium were:

• Bagchi, “Why are MYC-driven cancers so lethal?” 
• Liou, “Investigating the deposition of H3.3K27M oncohistone and its effect on retrotransposon reactivation in H3K27M pediatric diffuse midline glioma” 
• Ani Deshpande, PhD, associate professor in the Cancer Genome and Epigenetics Program and associate director of Diversity, Equity and Inclusion in the NCI-Designated Cancer Center, “Functional genomic approaches to identify selective dependencies in synovial sarcoma” 
• Peter D. Adams, PhD, the director of the Cancer Genome and Epigenetics Program, “The role of aging in cancer” 
• Lukas Chavez, PhD, associate professor in the Cancer Genome and Epigenetics Program, “Circular extrachromosomal DNA promotes tumor heterogeneity and enhancer rewiring” 
• Jerold Chun, MD, PhD, professor in the Degenerative Diseases Program, “Genetic mosaicism and somatic gene recombination in the brain” 
• Adarsh Rajesh, graduate student, Sanford Burnham Prebys, “CCND1-CDK6 complex inhibits DNA damage repair and promotes inflammation in senescence and the aged liver”

Additional speakers included:

• Taylor, “Why does medulloblastoma love to be tetraploid and other nonsense”
• Jabado, “Co-opting 3D structures to fuel tumorigenesis”
• Tannishtha Reya, PhD, Herbert and Florence Irving Professor of Basic Science Research in Physiology and Cellular Biophysics, Columbia University, “New genetically engineered models to understand cancer heterogeneity and therapy resistance in pancreatic cancer”
• Simona Dalin, PhD, postdoctoral fellow, Broad Institute of the Massachusetts Institute of Technology and Harvard University, “Contributions of perfect and imperfect homology to rearrangement formation in human and cancer genomes”
• Alison M. Taylor, PhD, assistant professor of Pathology and Cell Biology, Columbia University, “Functional and computational approaches to uncover the consequences of chromosome arm aneuploidy in cancer”
• Sean Eagan, PhD, senior scientist in the Cell Biology program at The Hospital for Sick Children, professor of Molecular Genetics, University of Toronto, “An update on Genetic analysis of 16q-syntenic block deletion in the mouse mammary gland – a tumor suppressor arm”
• Claudia Kleinman, PhD, associate professor of Human Genetics, McGill University, investigator at the Lady Davis Institute for Medical Research, Jewish General Hospital, “Lineage programs and the 3D genome in pediatric brain tumors”
• Branden Moriarity, PhD, associate professor of Pediatrics (Hematology and Oncology), University of Minnesota Medical School, “Next generation engineered immune effector cells for immunotherapy”
• Beau Webber, PhD, associate professor of Pediatrics (Hematology and Oncology), University of Minnesota Medical School, “Building cancer in a dish: Sarcoma modeling using human pluripotent stem cells”
• Sameer Agnihotri, PhD, associate professor of Neurological Surgery and director of the Brain Tumor Biology and Therapy Lab, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, “Identifying genetic vulnerabilities by modeling Chromosome 9p loss”
• Largaespada, “Loss of the polycomb repressor complex 2 (PRC2) alters the super-enhancer landscape, genome/epigenome stability, and therapeutic sensitivities of malignant peripheral nerve sheath tumors”
• Teresa Davoli, PhD, assistant professor of Biochemistry and Molecular Pharmacology, New York University Langone Health, “Engineering chromosome specific aneuploidy by targeting human centromeres”
• Rameen Beroukhim, MD, PhD, associate professor of Medicine, Dana-Farber Cancer Institute and Harvard Medical School, associate member of the Broad Institute of MIT and Harvard, “Detecting rearrangement signatures—naturally”
• Quang Trinh, PhD, scientist, Ontario Institute for Cancer Research, “Perspectives and Challenges in PFA Integrative Analysis”
• Taylor Gatesman, graduate student, University of Pittsburgh, “Genome Engineering: DREaming of and vCREating new models”
• Joseph Skeate, PhD, postdoctoral fellow, University of Minnesota Medical School, “Targeted CAR integration and multiplex base editing in a single-step manufacturing process for enhanced cancer immunotherapies”

Sanford Burnham Prebys scientist Peter Adams planned the symposium in partnership with colleagues at the University of California San Diego and Altos Labs.

Researchers gathered in San Diego from September 10-11 to discuss their research findings on the causes and complications of aging at the level of the trillions of cells in our bodies—and the vast array of molecules within each cell.

Peter D. Adams, PhD, the director of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, was one of the planners of the meeting, which was held at the Estancia La Jolla Hotel and Spa. Adams’ co-planners were Bing Ren, PhD, professor of Cellular and Molecular Medicine at the University of California San Diego, and Morgan Levine, PhD, founding principal investigator at the Altos Labs’ San Diego Institute of Science.

Before the 2024 Molecular and Cellular Aging Meeting kicked off, attendees were welcomed to join the final proceedings of a related meeting of the Cellular Senescence Network (SenNet) Consortium, a large network of U.S. labs and research institutions supported by the National Institutes of Health’s Common Fund.

Adams introduced Ashley Webb, PhD, associate professor at the Buck Institute for Research on Aging in Novato, Calif., to give the SenNet meeting’s Judy Campisi Lecture Series keynote address. This series of lectures honors Campisi’s legacy as a leader in the field of cellular senescence, a phenomenon closely tied with aging in which certain cells stop growing and dividing yet persist in a zombie-like state.

Following Webb’s lecture, Adams formally opened the 2024 Molecular and Cellular Aging Meeting. The event featured more than a dozen presentations and several poster sessions.

“I was excited to see the room so full in anticipation of the great talks and all the fantastic questions and discussion that followed,” said Adams.

“I am happy that we achieved our goal of bringing together SenNet reseachers and other leaders in the molecular and cellular biology of aging. I expect that this catalyzed many new ideas and collaborations.”

Speakers at the event included:

• Vittorio Sebastiano, PhD, associate professor of Obstetrics and Gynecology (Reproductive and Stem Cell Biology), Stanford University School of Medicine, “Looking at aging and rejuvenation through the lens of development and reproductive biology”
• Zhijian “James” Chen, PhD, Howard Hughes Medical Institute investigator, George L. MacGregor Distinguished Chair in Biomedical Science and professor of Molecular Biology, University of Texas Southwestern Medical Center, “Igniting the flame—the role of cGAS in senescence and inflammaging”
• Vera Gorbunova, PhD, Doris Johns Cherry Professor and professor of Biology, University of Rochester, “Epigenome maintenance and longevity”
• Jan Karlseder, PhD, senior vice president, chief science officer, professor in the Molecular and Cell Biology Laboratory and Donald and Darlene Shiley Chair, Salk Institute, “How telomeres synergize with mitochondria to prevent age associated cancer initiation”
• Shelley L. Berger, PhD, Daniel S. Och University Professor, University of Pennsylvania, “Epigenetic-metabolic crosstalk in senescence and aging” 
• Levine, “Origins of Life and Death: Aging as an Out-of-Distribution Problem”
• Adams, “The role of aging in cancer”
• Kun Zhang, PhD, principal investigator, Altos Labs’ San Diego Institute of Science, “An aging and injury cell atlas of human kidneys”
• Nancy R. Zhang, PhD, Ge Li and Ning Zhao Professor, professor of Statistics and Data Science and vice dean of Wharton Doctoral Programs, University of Pennsylvania, “Transcriptomic signatures of senescence and aging” 
• Alex Cagan, PhD, assistant professor of Genetics, Pathology and Veterinary Medicine, University of Cambridge, “Somatic evolution and ageing across the tree of life”
• Congcong He, PhD, associate professor of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, “Exercise-induced autophagic protection against age-related metabolic diseases”
• Gerald Shadel, PhD, professor in the Molecular and Cell Biology Laboratory, Audrey Geisel Chair in Biomedical Science and director of the San Diego-Nathan Shock Center of Excellence in the Basic Biology of Aging, Salk Institute, “Mitochondrial stress signaling in aging, disease and immunity”

Peter Adams, PhD

Bing Ren, PhD

Morgan Levine, PhD

Golgi apparatus

The Golgi apparatus or complex, named after its discoverer Camillo Golgi, functions as a factory and distribution warehouse in which proteins received from the endoplasmic reticulum, part of a cells transportation system, are further processed and sorted for shipment to their eventual destinations.

The organelle looks like a set of stacked membranes. Here, incoming proteins might be paired with carbohydrates (a sort of sugar frosting) to create so-called glycoproteins, which serve many functions in the body, from providing structure (such as collagens) to acting as antibodies to hormonal activities.

The process of creating glycoproteins is called glycosylation. It’s an extraordinarily complex process involving more than 500 genes and when some are defective, a group of metabolic diseases called Congenital Disorders of Glycosylation (CDG) result. Roughly 200 types of CDG have been identified.

At Sanford Burnham Prebys, Hudson Freeze, PhD, specializes in CDGs as director of the Sanford Children’s Health Research Center. This large group of rare genetic disorders cause a wide array of health issues, mostly emerging in childhood, and often foretell an early death.

There are no known cures for CDGs, but clinical trials for novel therapies have been launched, providing real hope for better management of symptoms, improved quality of life and, ultimately, cures.

About the art: Odra Noel is a medical doctor and PhD in basic science, with additional degrees in aesthetics and music. Her silk paintings focus primarily on human biology, often informed by microscopy. Wellcome Collection.

Six young scientists at Sanford Burnham Prebys, whose research spans genetic disorders, Alzheimer’s disease, heart failure and aging, were honored September 17 at the 23^rd annual Fishman Fund awards ceremony.

The Fishman Fund was created in 2001 by Sanford Burnham Prebys supporters Mary Bradley and Reena Horowitz to honor Dr. William and Mrs. Lillian Fishman, who founded the institute in 1976. In 2010, Jeanne Jones became a co-founder designee.

The awards are intended to support and promote early career scientists at Sanford Burnham Prebys. Four career development awards provide $10,000 stipends that can be used to attend workshops, network and travel to national and international conferences to learn about the latest developments in their research fields. In addition, the prizes include a two-year fellowship award, and an honor focused on rewarding research excellence. The fund is made possible through the generosity of many donors.

The ceremony, which included poster presentations, was held at the Sanford Consortium for Regenerative Medicine. The 2024 recipients are:

Reena Horowitz and Mary Bradley Fishman Fund Award

Zinia D’Souza, PhD, is a postdoctoral associate in the laboratory of Hudson Freeze, PhD, director of the Sanford Children’s Health Research Center and the director of the Human Genetics Program.Her research is focused on identifying new congenital disorders of glycosylation (CDGs), rare disorders caused by mutations that impair glycosylation—the complex process by which cells build long sugar chains that are attached to proteins called glycoproteins. D’Souza also works to uncover how these rare genetic mutations cause the observed symptoms.

Don Barach Memorial Fishman Fund Award

Huijie Huang, PhD, is a postdoctoral associate in the lab of Timothy Huang, PhD, an assistant professor in the Degenerative Diseases Program. Her research focuses on uncovering the fundamental causes of Alzheimer’s disease AD), a pressing public health concern as the U.S. population ages and faces an increased risk of this leading cause of dementia. Specifically, she studies the SORL1 (SORLA) gene, a known risk factor for sporadic early- and late-onset AD. Huang believes that developing treatments to boost SORLA’s beneficial effects may prove to be an innovative treatment approach.

Fishman Fund Fellowship Award

James Marchant, PhD, is a postdoctoral associate in the lab of Alexandre Colas, PhD, an associate professor in the Development, Aging and Regeneration Program. His research focuses on developing a gene therapy to treat heart failure. Heart attacks reduce blood and oxygen flow to heart muscle, leading to scar tissue that can increase the risk of future attacks. Marchant aims to convert cells within this scar tissue back into healthy muscle cells.

Cynthia Schwartz Shenkman Fishman Fund Research Excellence Award

Chiara Nicoletti, PhD, is a postdoctoral associate in the laboratory of Pier Lorenzo Puri, MD, co-director of the Development, Aging and Regeneration Program. She studies epigenetic patterns, which are genetic changes that don’t alter DNA itself yet modify how genes are expressed to make proteins or other products. She studies epigenetic patterns in skeletal muscle development and disease. Nicoletti hopes to help develop personalized medicine tools for patients suffering from muscular dystrophy.

Jeanne Jones and Kathryn Fishback Fishman Fund  Award

Jessica Proulx, PhD, is a postdoctoral associate working in the lab of Peter D. Adams, PhD, director of the Cancer Genome and Epigenetics Program. Proulx investigates how aging alters our bodies at the cellular and molecular levels, a key factor in the increased risk for diseases such as cancer, neurodegenerative disorders, cardiovascular disease and metabolic conditions like type 2 diabetes. She uses biological techniques that study the entire landscape of a sample’s genes, proteins or other features. Her work seeks to identify underlying changes that predispose an aged liver to liver disease and liver cancer.

Lenka Finci and Erna Viterbi Fishman Fund Award

Kelly Yichen Li, PhD, is a postdoctoral associate in the lab of Kevin Yip, PhD, a professor in the Cancer Genome and Epigenetics Program and the director of the Bioinformatics Shared Resource. She studies a phenomenon called cellular senescence that is associated with aging. Senescent cells no longer grow and divide, which can reduce the growth of cancer, but the condition is also  associated with chronic inflammation and age-related diseases. Yichen LI is working to find molecular signatures of senescence to advance aging research, treatments and diagnostics.