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Gladstone Institutes is an independent, non-profit biomedical research organization whose focus is to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
,
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
and
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. Its researchers study these diseases using techniques of basic and
translational science Translational research (also called translation research, translational science, or, when the context is clear, simply translation) is research aimed at translating (converting) results in basic research into results that directly benefit humans. ...
. Another focus at Gladstone is building on the development of
induced pluripotent stem cell Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...
technology by one of its investigators, 2012 Nobel Laureate
Shinya Yamanaka is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyoto ...
, to improve drug discovery, personalized medicine and tissue regeneration. Founded in 1979, Gladstone is academically affiliated with the
University of California, San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It cond ...
(UCSF), and located adjacent to UCSF's Mission Bay campus. The organization comprises five major institutes, as well as multiple centers focused on various areas of research. The current president of the institute is Deepak Srivastava.


History

Gladstone Institutes was founded in 1979 as a research and training facility housed at
San Francisco General Hospital The Priscilla Chan and Mark Zuckerberg San Francisco General Hospital and Trauma Center (ZSFG) is a Public hospital in San Francisco, California, under the purview of the city's Department of Public Health. It serves as the only Level I Trauma Ce ...
. Under inaugural president Robert Mahley—a cardiovascular scientist recruited from the National Institutes of Healthhttp://www.pnas.org/content/103/15/5641/—the institutes was launched with a $8 million trust from the late commercial real estate developer, J. David Gladstone. In 2004 the Gladstone Institutes moved to a new facility in San Francisco's
Mission Bay, San Francisco Mission Bay is a neighborhood on the east side of San Francisco, California. It is bordered by China Basin to the north, Dogpatch to the south, and San Francisco Bay to the east. Originally an industrial district, it underwent development fuele ...
neighborhood. Dr. Mahley stepped down as president in 2010 to return to active research, and was replaced by R. Sanders Williams (former Dean of the School of Medicine at
Duke University Duke University is a private research university in Durham, North Carolina. Founded by Methodists and Quakers in the present-day city of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco and electric power industrialist James ...
). Deepak Srivastava became the institute's third president in January 2018. In 2011, the S.D. Bechtel, Jr. Foundation helped launch the Center for Comprehensive Alzheimer's Disease Research, while the Roddenberry Foundation helped launch the Roddenberry Stem Cell Center for Biology and Medicine. Also in 2011, the independent and philanthropic Gladstone Foundation formed with the mission of expanding the financial resources for the institutes.


Organizational structure

Gladstone Institutes consists of five institutes: * Institute of Cardiovascular Disease * Institute of Virology * Institute of Neurological Disease * Institute of Data Science & Biotechnology * Institute of Genomic Immunology Gladstone is also home to eight centers for researchers from different institutes to collaborate. These centers focus on stem and iPS cell research, as well as neurodegenerative disease research and therapeutics.


Research programs


Cardiovascular disease

Gladstone cardiovascular scientists research the spectrum of cardiovascular disease, utilizing developmental, chemical, and stem cell biology approaches, as well as genomics techniques, across a variety of research programs and institutes. Their research has included: * Determining the genetic factors of congenital birth defects in early heart development *Studying various methods to repair damaged hearts, including creating heart cells from skin samples and converting scar tissue into muscle. *Exploring human evolution and metabolism to understand the human genome, and illnesses at the cellular level. *Studying the effects of COVID-19 on the heart.


Virology and immunology

In 1991, Gladstone expanded its focus to include
virology Virology is the Scientific method, scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host (biology), ...
and
immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...
in response to the HIV/AIDS crisis. Since then the institute has also studied
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
,
Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, whe ...
, and
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
. In 2011, Gladstone launched a $25 million initiative around HIV and aging. Their research has included: *Leading the global
iPrEx iPrEx (from es, Iniciativa Profilaxis Pre-Exposición, "pre-exposure prophylaxis initiative") was a phase III clinical trial to determine whether the antiretroviral medication emtricitabine/tenofovir (as tenofovir disoproxil fumarate) could saf ...
study, which led to the FDA approval of Truvada for HIV prevention in 2012. *Participating as a member of the Martin Delaney Collaboratory to study HIV latency. *Studying the "accelerated aging" effects associated with HIV/AIDS. * Studying how HIV integrates and replicates within the body, and how it kills lymphoid CD4 T-cells, the fundamental cause of AIDS. In 2020, two new institutes were formed; the Gladstone Institute of Virology, and the Gladstone-UCSF Institute of Genomic Immunology, to study how viruses interact with human cells to cause disease. The Institute of Virology has been involved in research regarding the
COVID-19 virus Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a p ...
, including its long-term effects on the heart, and studying samples of SARS-CoV-2 variations appearing in California, and their resistances to the
Moderna Moderna, Inc. ( ) is an American pharmaceutical and biotechnology company based in Cambridge, Massachusetts that focuses on RNA therapeutics, primarily mRNA vaccines. These vaccines use a copy of a molecule called messenger RNA (mRNA) to produ ...
and
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
.


Neurological disease

Research at Gladstone focuses on major neurological diseases including:
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
,
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
,
frontotemporal dementia Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as ...
(FTD),
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
,
amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
(ALS, or Lou Gehrig's disease) and
multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
. This research incorporates animal models,
electrophysiology Electrophysiology (from Greek , ''ēlektron'', "amber" etymology of "electron"">Electron#Etymology">etymology of "electron" , ''physis'', "nature, origin"; and , '' -logia'') is the branch of physiology that studies the electrical properties of b ...
, behavioral testing and automated high-throughput analyses. In addition, Gladstone investigators seek to accelerate the movement of basic science discoveries into clinical trials with efforts to bridge the so-called "Valley of Death". The research features an emphasis on the common threads linking the various diseases and treatments for them. Current research programs include: * ''
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
and network disruption''. Studying how damage to neurons affects their ability to communicate through chemical and electrical signals, which manifests as sub-clinical
epileptic Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
-like seizures. Discovered a link between this process and many of the deficits linked to Alzheimer's disease. * ''Alzheimer's disease and
apolipoprotein E Apolipoprotein E (APOE) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular disease. APOE belongs to a family of fat-binding proteins called apolipoproteins. ...
(apoE)''. Uncovered the molecular pathways that link apoE and Alzheimer's disease, and identifying new drugs that counteract detrimental effects of apoE4—the most important genetic risk factor for Alzheimer's. * ''Alzheimer's disease and
tau Tau (uppercase Τ, lowercase τ, or \boldsymbol\tau; el, ταυ ) is the 19th letter of the Greek alphabet, representing the voiceless dental or alveolar plosive . In the system of Greek numerals, it has a value of 300. The name in English ...
''. Understanding how lowering brain levels of the protein tau improves memory and other cognitive functions in mice genetically engineered to mimic Alzheimer's disease. * ''
TDP-43 TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by the ''TARDBP'' gene. Structure TDP-43 is 414 amino acid residues long. It consists of 4 domains: an N-terminal d ...
''. Studying TDP-43, another protein that may contribute to diverse neurodegenerative disorders. * ''Protein aggregates and their role in neurodegenerative disease''. Helping to uncover the mystery behind protein aggregations—observed in
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
(
inclusion bodies Inclusion bodies are aggregates of specific types of protein found in neurons, a number of tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also found in muscle cells ...
),
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(
Lewy bodies Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside nerve cells affected by Parkinson's disease (PD), the Lewy body dementias ( Parkinson's disease dementia and dementia with Lewy bodies (DLB)), and ...
), and Alzheimer's disease (neurofibrillary tangles and amyloid-beta plaques)—discovering that rather than being the culprit of neuronal death, these aggregates are part of a defense mechanism that safely sequesters toxin proteins in the brain. * Investigating the network of brain cells that controls movement, and how its dysfunction leads to the symptoms of Parkinson's disease. * ''
Mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and synaptic dysfunction''. Studying mitochondria, the energy-producing subunits of cells, and their role in multiple neurodegenerative conditions, including Alzheimer's, Parkinson's and ALS. * researching how
autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
can help prevent the destruction of brain cells, and how the p75 neurotrophin receptor —a protein involved in the development of brain cells— plays unexpected roles in both Alzheimer's and Type 2 diabetes. * ''
Inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
and
neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
.'' Studying abnormal inflammatory responses by immune cells in the central nervous system—which may contribute to the progression of multiple sclerosis, neurodegenerative disorders and many other neurological conditions. * ''
Frontotemporal dementia Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present as ...
''. Showed a protein called progranulin prevents a type of brain cells from becoming "hyperactive". If not enough progranulin is available the hyperactivity can become toxic and result in extensive inflammation that kills brain cells and can lead to the development of FTD. Also showed that too much of another protein called TDP-43 plays a role in FTD disease progression. Importantly, Gladstone scientists have identified a means to suppress the toxic effects of TDP-43 for FTD and for another neurodegenerative disease:
ALS Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most com ...
.


Stem cell technology

Another focus at Gladstone is building on the development of
induced pluripotent stem cell Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in ...
technology by one of its senior investigators, 2012 Nobel Laureate
Shinya Yamanaka is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyoto ...
. In 2006, Yamanaka discovered the technology, by which ordinary differentiated adult cells (such as
fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...
from skin) could be "reprogrammed" into a
pluripotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
state—i.e., a state similar to
embryonic stem cells Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they co ...
, which are capable of developing into virtually any cell type in the human body. His discovery of induced pluripotent stem cells, or iPS cells, has since revolutionized the fields of developmental biology, stem cell research and both personalized and regenerative medicine. In 2012 Yamanaka was awarded the Nobel Prize in Physiology or Medicine. Since Yamanaka's discovery, scientists at Gladstone have used iPS technology to research solutions for Huntington's disease and Alzheimer's disease, as well as create a new model for testing HIV/AIVD vaccines. Other work at the Data Science & Biotechnology Institute include: * Reprogramming cardiac connective tissue located in the heart directly into beating cardiac muscle cells. * Discovering new ways to use chemical compounds to convert cells from one type into another. * Direct reprogramming of cells into
neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
and neural precursor cells. * Using
iPS cells IPS, ips, or iPS may refer to: Science and technology Biology and medicine * ''Ips'' (genus), a genus of bark beetle * Induced pluripotent stem cell or iPS cells * Intermittent photic stimulation, a neuroimaging technique * Intraparietal sulcu ...
to create human models to research solutions for
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
and
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
. * Studying whether the
retrotransposons Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...
(also known as "jumping genes", because they move around within the chromosomes of a single cell) residing in our DNA become more active when a skin cell is reprogrammed into an iPS cell.


Translational research

The Gladstone Center for Translational Advancement was formed in 2017, and focuses on
drug repositioning Drug repositioning (also called drug repurposing) involves the investigation of existing drugs for new therapeutic purposes. Repurposing achievements A number of successes have been achieved, the foremost including sildenafil (Viagra) for ere ...
; repurposing already-approved drugs for new uses and clinical trials, to speed up (and lower the cost of) drug development.


Researchers

Researchers at the institute include: * Katerina Akassoglou, PhD — Senior Investigator * Benoi Bruneau, PhD — Director, Gladstone Institute of Cardiovascular Disease * Bruce Conklin, MD — Senior Investigator * Sheng Ding, PhD — Senior Investigator *
Jennifer Doudna Jennifer Anne Doudna (; born February 19, 1964) is an American biochemist who has done pioneering work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. Doudna was one of the first women to share a ...
, PhD — Senior Investigator. Awarded the 2020
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
. * Barbara Engelhardt, PhD — Senior Investigator * Steve Finkbeiner, MD, PhD— Director, Center for Systems and Therapeutics * Warner Greene, MD, PhD — Director, Center for HIV Cure Research * Yadong Huang MD, PhD — Senior InvestigatorChengzhong Wang, Ramsey Najm, Qin Xu, Dah-eun Jeong, David Walker, Maureen E. Balestra, Seo Yeon Yoon, Heidi Yuan, Gang Li, Zachary A. Miller, Bruce L. Miller, Mary J. Malloy & Yadong Huang. Gain of toxic Apolipoprotein E4 effects in Human iPSC-Derived Neurons Is Ameliorated by a Small-Molecule Structure Corrector. Nature Medicine, 2018 DOI: 10.1038/s41591-018-0004-z * Anatol Kreitzer, PhD — Senior Investigator * Nevan Krogan, PhD — Senior Investigator * Robert W. Mahley, MD, PhD — President emeritus and Senior Investigator * Alex Marson, MD, PhD — Director, Gladstone-UCSF Institute of Genomic Immunology * Todd McDevitt, PhD — Senior Investigator * Lennart Mucke, MD — Director, Gladstone Institute of Neurological Disease * Melanie Ott, MD, PhD — Director, Gladstone Institute of Virology *
Katherine Pollard Katherine Snowden Pollard is the Director of the Gladstone Institute of Data Science and Biotechnology and a professor at the University of California, San Francisco (UCSF). She is a Chan Zuckerberg Biohub Investigator. She was awarded Fellowsh ...
, PhD — Director, Gladstone Institute of Data Science and Biotechnology * Deepak Srivastava, MD — President, Gladstone Institutes *
Leor Weinberger Leor S. Weinberger is an American virologist and quantitative biologist. He is credited with discovering the HIV virus latency circuit, which provided the first experimental evidence that stochastic fluctuations ('noise') in gene expression a ...
, PhD — Senior Investigator *
Shinya Yamanaka is a Japanese stem cell researcher and a Nobel Prize laureate. He serves as the director of Center for iPS Cell (induced Pluripotent Stem Cell) Research and Application and a professor at the Institute for Frontier Medical Sciences at Kyoto ...
— MD, PhD — Senior Investigator. Awarded the 2012
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
.


References


External links


Official site
{{authority control Independent research institutes Research institutes Medical research institutes in California Research institutes in the San Francisco Bay Area University of California, San Francisco