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Institute News

Top Sanford Burnham Prebys research stories of 2021

AuthorSusan Gammon
Date

December 14, 2021

top 10 sign

This year’s most popular research stories include scientific breakthroughs in COVID-19, cancer, schizophrenia and more.

As we bid farewell to 2021, let’s celebrate our most newsworthy research breakthroughs. Despite the continuing challenges brought on by COVID-19, Sanford Burnham Prebys achieved important milestones on the frontiers of biomedical science.

The following 10 research-related stories received top views on Newswise—the press release distribution service for journalists seeking health and science news.
 

  1. COVID-19: Scientists identify human genes that fight infection
    A research team was able to pinpoint specific human genes that control viral infection. The information sheds new light on factors that lead to severe disease and guides therapeutic options.
     
  2. Tumor marker may help overcome endocrine treatment-resistant breast cancer
    The study discovered a new approach to select breast cancer patients for HER2 therapy and could help individuals avoid disease relapse or progression of endocrine-sensitive disease.
     
  3. Scientists identify potential drug candidates for deadly pediatric leukemia
    Two existing drugs—JAK inhibitors and Mepron—show promise for a subtype of acute myeloid leukemia (AML) that is more common in children. The drugs are proven safe in humans, which could accelerate clinical studies.
     
  4. Leprosy drug holds promise as at-home treatment for COVID-19
    Scientists found that the leprosy drug clofazimine, which is FDA approved and on the World Health Organization’s List of Essential Medicines, exhibits potent antiviral activities against SARS-CoV-2, and could become an important weapon against future pandemics.
     
  5. Researchers dig deeper into how cells transport their waste for recycling
    Research describing how the “trash bags” in a cell—called autophagosomes—are tagged for recycling opened new paths to understand age-related diseases such as cancer and neurological disorders.
     
  6. New drug combination shows promise as powerful treatment for AML
    Researchers identified two drugs that are potent against acute myeloid leukemia (AML) when combined, but only weakly effective when used alone. The study provides a scientific rationale for advancing clinical studies of the drug combination.
     
  7. Biomarker could help diagnose schizophrenia at an early age
    A study described how elevated levels of a protein called CRMP2—found in the brain and blood—could become a format for a rapid, minimally invasive blood test to support the diagnosis of schizophrenia.
     
  8. Scientists identify “immune cop” that detects SARS-CoV-2
    Researchers discovered the sensor in human lungs that detects SARS-CoV-2 and signals that it’s time to mount an antiviral attack. The sensor activates interferon, the body’s own frontline defender against viral invasion.
     
  9. Study finds promising therapeutic target for colitis
    Scientists identified an enzyme in the gut that triggers an inflammatory cascade leading to colitis. Therapeutically targeting the enzyme may be a viable approach to help the millions of people worldwide affected by the disorder.
     
  10. Scientists shrink pancreatic tumors by starving their cellular “neighbors”
    For the first time, blocking “cell drinking,” or micropinocytosis in the thick tissue surrounding a pancreatic tumor, was shown to slow tumor growth—providing more evidence that micropinocytosis is an important therapeutic target.
Institute News

Brain map connects brain diseases to specific cell types

AuthorSusan Gammon
Date

January 8, 2018

Astrocyte cells

Researchers have developed new single-cell sequencing methods that could be used to map the cell origins of various brain disorders, including Alzheimer’s, Parkinson’s, schizophrenia and bipolar disorder.

By analyzing individual nuclei of cells from adult human brains, Jerold Chun, MD, PhD, professor at SBP, in collaboration with researchers at UC San Diego and Harvard Medical School, have identified 35 different subtypes of neurons and glial cells and discovered which of these subtypes are most susceptible to common risk factors for different brain diseases.

There are multiple theories regarding the roots of brain diseases. The new study, published in Nature Biotechnology, allows scientists to narrow down and rank the cell types in the brain that carry the most genetic risk for developing brain disorders. The information can guide researchers to pick the best drug-targets for future therapies.

The work builds off of a previous study by the authors that identified 16 subtypes of neurons in the cerebral cortex. That study was the first large-scale mapping of gene activity in the human brain and provided a basis for understanding the diversity of individual brain cells.

In the new study, researchers developed a new generation of single-cell sequencing methods that enabled them to identify additional neuronal subtypes in the cerebral cortex as well as the cerebellum, and even further divide previously identified neuronal subtypes into different classes. The new methods also enabled researchers to identify different subtypes of glial cells, which wasn’t possible in the previous study due to the smaller size of glial cells.

“These data confirm and significantly expand our prior work, further highlighting the enormous transcriptional diversity among brain cell types, especially neurons,” says Chun. “This diversity, which continues to emerge from our single-cell analytical approach, will provide a foundation for better understanding the normal and diseased brain.” The advance was made possible by combining next-generation RNA sequencing with chromatin mapping—mapping of DNA and proteins in the nucleus that combine to form chromosomes—for more than 60,000 individual neurons and glial cells.

“While the analysis of RNA can tell us how cell types differ in their activity, the chromatin accessibility can reveal the regulatory mechanisms driving the distinctions between different cells”, notes Peter Kharchenko, PhD, an assistant professor of biomedical informatics at Harvard Medical School who co-led the study.

Using the information from RNA sequencing and chromatin mapping methods, researchers were able to map which cell types in the brain were affected by common risk alleles—snippets in DNA that occur more often in people with common genetic diseases. Researchers could then rank which subtypes of neurons or glial cells are more genetically susceptible to different brain diseases. For example, they found that two subtypes of glial cells, microglia and oligodendrocytes, were the first and second most at risk, respectively, for Alzheimer’s disease. They also identified microglia as most at risk for bipolar disorder, and a subtype of excitatory neurons as most at risk for schizophrenia.

“Now we can locate where the disease likely starts,” says Kun Zhang, PhD, professor of bioengineering at the UC San Diego Jacobs School of Engineering and co-senior author of the study. “However, we are only mapping the genetic risk. We don’t know the precise mechanism of how these specific cells actually trigger the disease.”

One caveat of this study, explains Zhang, is that it primarily analyzed data from adult brains (ages 20 to 50), so the findings do not represent younger or older populations. In order to better understand brain disorders that manifest early on, for example in infants, like autism spectrum disorder, the study would need to analyze cells from younger brains, he said.

The team also plans to expand their studies to map additional regions of the brain.

Authors of the study are Blue B. Lake*, Song Chen*, Brandon C. Sos*, Thu E. Duong, Derek Gao and Kun Zhang of UC San Diego; Jean Fan* and Peter V. Kharchenko of Harvard Medical School; and Gwendolyn Kaeser, Yun C. Yung and Jerold Chun of Sanford Burnham Prebys Medical Discovery Institute.

*These authors contributed equally to this work.

This story is based on a UC San Diego press release written by Liezel Labios.

Institute News

Consortium awarded $15 million to unravel bipolar disorder and schizophrenia

AuthorSusan Gammon
Date

August 31, 2016

Anne Bang, PhD

Sanford Burnham Prebys Medical Discovery Institute (SBP), the Johns Hopkins University School of Medicine, the Salk Institute for Biological Studies, and the University of Michigan will embark on a $15.4 million effort to develop new systems for quickly screening libraries of drugs for potential effectiveness against schizophrenia and bipolar disorder, the National Institute of Mental Health (NIMH) has announced. The consortium, which includes two industry partners, will be led by Hongjun Song, PhD, of Johns Hopkins and Rusty Gage, PhD, of Salk.

Bipolar disorder affects more than 5 million Americans, and treatments often help only the depressive swings or the opposing manic swings, not both. And though schizophrenia is a devastating disease that affects about 3 million Americans and many more worldwide, scientists still know very little about its underlying causes — which cells in the brain are affected and how — and existing treatments target symptoms only.

With the recent advance of induced pluripotent stem cell (iPSC) technology, researchers are able to use donated cells, such as skin cells, from a patient and convert them into any other cell type, such as neurons. Generating human neurons in a dish that are genetically similar to patients offers researchers a potent tool for studying these diseases and developing much-needed new therapies.

“IPSCs are a powerful platform for studying the underlying mechanisms of disease,” says Gage, a professor of genetics at Salk. “Collaborations that bring together academic and industry partners, such as this one enabled by NIMH, will greatly facilitate the improvement of iPSC approaches for high-throughput diagnostic and drug discovery.”

A major aim of this collaboration is to improve the quality of iPSC technology, which has been limited in the past by a lack of standards in the field and inconsistent practices among different laboratories. “There has been a bottleneck in stem cell research,” says Gage, a professor of genetics at Salk. “Every lab uses different protocols and cells from different patients, so it’s really hard to compare results. This collaboration gathers the resources needed to create robust, reproducible tests that can be used to develop new drugs for mental health disorders.”

The teams will use iPSCs generated from more than 50 patients with schizophrenia or bipolar disorder so that a wide range of genetic differences is taken into account. By coaxing iPSCs to become four different types of brain cells, the teams will be able to see which types are most affected by specific genetic differences and when those effects may occur during development.

First the researchers must figure out, at the cellular level, what features characterize a given illness in a given brain cell type. To do that, they will assess the cells’ shapes, connections, energy use, division and other properties. They will then develop a way of measuring those characteristics that works on a large scale, such as recording the activity of cells under hundreds of different conditions simultaneously.

“SBP’s Conrad Prebys Center for Chemical Genomics will play a key role in this initiative,” says Anne Bang, PhD, a director at the Center. “We will be developing assays and testing prototype drug compounds to see if they induce the desired response in iPSC disease models from the consortium. Our goal is to establish assays suitable for high throughput drug screening, ultimately leading to discovery of drugs for preclinical and clinical studies.”

Once a reliable, scalable and reproducible test system has been developed, the industry partners will have the opportunity to use it to identify or develop drugs that might combat mental illness. “This exciting new research has great potential to expedite drug discovery by using human cells from individuals who suffer from these devastating illnesses. Starting with a deeper understanding of each disorder should enable the biopharmaceutical industry to design drug discovery strategies that are focused on molecular pathology,” says Husseini K. Manji, MD, F.R.C.P.C., global therapeutic area head of neuroscience for Janssen Research & Development.

The researchers also expect to develop a large body of data that will shed light on the molecular and genetic differences between bipolar disorder and schizophrenia. And, since other mental health disorders share some of the genetic variations found in schizophrenia and bipolar disorder, the data will likely inform the study of many illnesses.

The National Cooperative Reprogrammed Cell Research Groups program, which is funding the research, was introduced by the National Institute of Mental Health in 2013 to overcome barriers to collaboration by creating precompetitive agreements that harness the unique strengths of academic and industry research.