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.

The scholarship program for graduate students was created by the Clause family’s generous donation to Sanford Burnham Prebys.

Michael Alcaraz, a fourth-year graduate student in the Sanford Burnham Prebys Graduate School of Biomedical Sciences, was selected as the 2024 recipient of the Melvin and Phyllis McCardle Clause Scholarship.

“I am very excited about being chosen for this scholarship,” said Alcaraz. “I’ll be gaining mentorship opportunities from researchers in neuroscience that complement my lab’s focus on aging.

“This funding will make a big difference as my research moves forward. The scholarship also provides support for professional development, which will allow me to attend conferences to share what I’m studying and grow my network.”

The McCardle Clause Scholarship was established in honor of Phyllis McCardle Clause after her long struggle with Alzheimer’s disease (AD). The award supports graduate student education in age-related neurodegeneration within the Institute’s graduate school.

Alcaraz conducts research in the laboratory of Peter D. Adams, PhD, the director of the Cancer Genome and Epigenetics Program, with a focus on the mechanisms of aging.

With support from the scholarship, Alcaraz will be investigating the fundamental connections between aging and the increased risk of AD, the most common cause of dementia. His project is focused on the role of nicotinamide adenine dinucleotide (NAD+), an essential metabolite and building block for enzymes.

NAD+ levels decrease with age in several tissues, including in the brains of humans and mouse models of AD. The decline of this important metabolite is associated with insufficient energy metabolism that is a major hallmark of AD.

“In collaboration with the Conrad Prebys Center for Chemical Genomics, we will test a potential drug to promote production of NAD+ in the brain by activating a key enzyme involved in NAD+ biosynthesis,” said Alcaraz.  The compound was developed by the Conrad Prebys Center for Chemical Genomics led by Michael Jackson, PhD, senior vice president of Drug Discovery and Development.

“The goal of my project is to raise the levels of NAD+ in mice suffering from an analogous condition to AD and test its effects on improving brain metabolism, function and behavior,” added Alcaraz.

“The objective is to build the preclinical foundation for one day achieving benefits for patients. We all know how devastating AD is for patients and families, and the need for new treatments grows greater every single day.

“This project will require a lot of collaboration between experts in aging, drug discovery, neuroscience and behavioral analysis. We have all this expertise available across the Institute, and I’m looking forward to working with an interdisciplinary team on this effort thanks to the generosity of the Clause family.”

This annual award was established in 2024 to recognize the contributions of postdoctoral fellows at Sanford Burnham Prebys.

Chiara Nicoletti, PhD, a postdoctoral associate at Sanford Burnham Prebys, was selected as the first recipient of the Fishman Fund Cynthia Schwartz Shenkman Research Excellence Award. 

This award is one of two new honors being given during the 23^rd Fishman Funds awards ceremony on September 17, marking 2024 as a special year for the Institute and the supporting donors.  

The inaugural Don Barach Fishman Fund Career Award adds a fourth prize in the category of career awards focused on providing professional development opportunities for postdoctoral fellows. In addition, the Fishman Fund Cynthia Schwartz Shenkman Research Excellence Award adds a new third category of honors.  

This award recognizes and rewards experienced postdoctoral fellows who have achieved a track record of research excellence. It is designed to help offset the cost of living in the region, and to benefit recipients as they prepare for the next step in their careers.

“For me, this award provides recognition of my hard work and that of my colleagues,” said Nicoletti. “It also acknowledges my mentor at Sanford Burnham Prebys and how he supports members of his laboratory.”

Nicoletti studies epigenetic patterns in skeletal muscle development and disease in the laboratory of Pier Lorenzo Puri, MD, director of the Development, Aging and Regeneration Program.

“My graduate school mentor met Lorenzo at a conference in 2016,” said Nicoletti. “Lorenzo wanted to apply what was then a very new technique called Hi-C to better understand how the MyoD protein—a key player in the establishment of muscle cell identity—is able to transform non-muscle cells into muscle.

“He wanted to study how changes in the three-dimensional organization of DNA can trigger alterations in gene expression, leading to a switch in cell identity. Few people in the world could analyze the data from these experiments at that time. And one of those people was me.”

Chiara’s accomplishments since joining Sanford Burnham Prebys and the Puri lab in 2018 include her work on dysferlinopathy, a rare form of muscular dystrophy. In collaboration with the laboratory of Jyoti K. Jaiswal, MSc, PhD, at Children’s National Research Institute in Washington, D.C., she developed an atlas mapping how the disease causes changes in the transcription of genes in skeletal muscle. This compendium follows the disease progression of dysferlinopathy at the single-cell level.

Dysferlinopathy patients suffer from progressive muscle loss in which muscle cells are replaced by fat and scar tissue. Understanding how this process takes place may accelerate research to find new drugs to improve muscle function. For her work on this project, Nicoletti was recently recognized with the Young Investigator Award by the Jain Foundation, a nonprofit foundation focused on finding a cure for dysferlinopathy.

“When you get to know people with muscular dystrophy, you immediately see that their minds are bursting with life,” reflected Nicoletti. “Someone I met recently said his dream was to bring his daughter to the altar at her wedding and have a father-daughter dance. If we can do something to improve his quality of life, imagine the ripple effects of what that would mean to his daughter, to his whole family.”

When Nicoletti completes her postdoctoral fellowship, she would like to remain in academia as an independent principal investigator.

“As a bioinformatician with experience in bench research, I hope to bring different labs together to build interdisciplinary collaborations focused on how diverse biological systems and organs interact.

“I also would like to teach as I feel it is our fundamental duty as scientists to train the next generation. I believe it is especially important to educate students and postdoctoral fellows about basic bioinformatics skills so that they are better equipped to evaluate published data and collaborate with computational biologists.”

Nicoletti also expressed a long-term goal of applying computational biology methods to advance knowledge of why patients are more or less susceptible to disease and have different responses to medications. These learnings are critical to personalizing treatment plans for individuals rather than populations.

Nicoletti is thankful for the support of the Fishman Fund Cynthia Schwartz Shenkman Research Excellence Award during the remainder of her postdoctoral training.

“The work I do is very rewarding. It feels close to the best that humanity has to offer when scientists and patients collaborate to achieve a common goal.

“I’m so grateful for this award, which serves as even more motivation for me, my mentor and collaborators. We’re each only given one life, and I’m determined to give back as much as I can to society through science.”

Protein pore

Nuclear pores are protein-lined channels connecting the inner nucleus of a eukaryotic cell with the surrounding cytoplasm—the gelatinous liquid that fills the inside of the cell, giving it shape and protection.

Nuclear pores allows small molecules and ions to freely diffuse into or out of the nucleus, giving passage to critical information and materials for cell functions.

At Sanford Burnham Prebys, Maximiliano D’Angelo, PhD, and Valeria Guglielmi, PhD, are investigating how nuclear pores in cancer cells are different and how these differences contribute to malignancy and tumor development. By better understanding  the functions of nuclear pores in healthy and cancerous cells, they hope to develop novel therapies that target the development and progression of cancer at the cellular level.

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.

Congratulations to Sanford Burnham Prebys President and CEO David Brenner, who received last night the 2024 Director of the Year award in the category of “companies in transition” from the Corporate Directors Forum, a San Diego-based network of top executives.

The award was presented in ceremonies at the Hyatt Regency in La Jolla.

Brenner, who became president and CEO of Sanford Burnham Prebys in September 2022, was honored for his bold and dramatic vision of the institute as a 21^st century leader in biomedical research.

“This award is given to directors who have contributed significantly in times of change and have brought positive and productive conclusions,” said Lori Moore, a former award recipient and Sanford Burnham Prebys trustee in her introduction at the event.

“David is both passionate and humble. He is both a physician and a scientist. Most importantly, David leads a cultural shift at Sandford Burnham Prebys with tenacity, passion, and humility! He has brought in exceptional new scientists and restructured the organization. His passion is to create a culture in our community where people synergize and find resources to work together. He indeed translates science into health.”

In just two years, Brenner has restructured the institute as home to four disease-focused centers (cancer, cardiovascular, neurologic and metabolic) and three technology-enabling centers for drug discovery, multi-omics and artificial intelligence.

With a landmark $70 million gift from philanthropist T. Denny Sanford, he has recruited a dozen new and established scientists.

“The old ways of thinking about and doing science no longer adequately address the complexities of modern science or the realities of the public health challenges we face,” said Brenner. “As scientists and physicians, we must transform how we work even as our work continues to transform itself.”