The Center for Cell Circuitry addresses the enormous therapeutic potential of cellular circuits, which connect individual molecular components and allow cells to process signals and control decision-making.
The center creates single-cell tools to map how cellular components connect into circuits. The center also develops new approaches that overcome inherent limitations in traditional techniques, which analyze bulk populations of cells, thereby obscuring individual cell behavior. Ultimately, the center’s goal is to control these circuits through therapeutic targeting in a variety of biological systems, including cellular reprogramming, neuroscience, cancer, and infectious disease.
Center for Comprehensive Alzheimer’s Disease Research
In 2011, the S.D. Bechtel, Jr. Foundation helped launch the Center for Comprehensive Alzheimer’s Disease Research at Gladstone with a generous $6M lead gift. This investment is helping Gladstone scientists more quickly develop therapies for those suffering from Alzheimer’s, or who are at increased risk of getting the disease. Currently, the field lacks effective medications to prevent, halt or reverse this devastating illness.
The Center taps Gladstone’s unique expertise in neurodegenerative diseases. In recent years, for instance, Gladstone scientists demonstrated how amyloid proteins that build up in brains of Alzheimer patients disrupt cognitive processes such as memory—and how this process may be prevented and reversed. We have also established one of the world’s leading drug-development programs targeting Alzheimer’s main genetic risk factor. Last year, Gladstone scientists announced a promising new drug candidate that prevents memory deficits and the loss of synaptic connections between brain cells—key features of Alzheimer’s—in mice modeling the disease.
Since the establishment of this Center, some of its most promising research efforts have been leveraged into collaborations with leading pharmaceutical companies, including Bristol-Myers Squibb and Takeda Pharmaceuticals.
Center for HIV Cure Research
The Gladstone Center for HIV Cure Research seeks to build upon the past success of the Gladstone Institute of Virology and Immunology, but with a singular research focus: to identify, reduce, and control latent HIV reservoirs to allow infected individuals to eventually discontinue antiretroviral therapy. The center is directed by Warner C. Greene, MD, PhD, who is also co-director of the UCSF-Gladstone Center for AIDS Research, as well as a principal investigator and member of the board of directors of the amfAR Institute for HIV Cure Research at UCSF.
The “reduce and control” strategy involves decreasing the size of HIV reservoirs while engineering an immune response to control the remaining virus. While it does not fully eradicate the virus, this strategy find precedence in a small group of individuals termed “elite controllers” who are able to control HIV without the need for antiretroviral drugs.
The scientists will search for potent and nontoxic ways to wake up the latent virus, in order to precisely define the types of cells that comprise the reservoirs and allow for contraction of the reservoirs. They will also examine the role of resident memory CD4 T cells that do not circulate in the blood stream and T-follicular helper cells that chiefly reside in lymphoid follicles as reservoirs for latent virus. Interestingly, CD8 and NK cells are unable to traffic into lymphoid follicles. So, these killer cells will likely be needed to reduce the size of the reservoir.
The center will also pursue novel approaches to identify biomarkers for latently-infected reservoir cells. In general, only one latently infected CD4 T cell is present within 1 million CD4 T cells. Thus, cells participating in the latent reservoir are rare and currently cannot be purified because no biomarkers have been identified. In addition to allowing the purification of latently infected cells, such biomarkers could provide new therapeutic insights.
Members include Melanie Ott, Nadia Roan, Shomyseh Sanjabi, and Leor Weinberger. In addition, investigators from the Division of Experimental Medicine at UC San Francisco, the amfAR Institute for HIV Cure Research, and the Blood Systems Research Institute actively collaborate with this center.
Center for In Vivo Imaging Research (CIVIR)
In 2010, the Gladstone Institutes established the Center for In Vivo Imaging Research (CIVIR). CIVIR’s mission is to develop technologies to investigate the dynamic interactions between the immune, vascular and nervous systems as a way to better understand the origins and progress of neurological diseases. We plan to use these techniques to design and test effective treatments for these diseases.
Katerina Akassoglou, PhD, is CIVIR’s founding Director while Dimitrios Davalos, PhD, serves as Associate Director. Different funding sources contributed to the establishment of CIVIR, including the international pharmaceutical company H. Lundbeck A/S, the S.D. Bechtel, Jr. Foundation and an anonymous donor.
Center for Systems and Therapeutics
In contrast to reductionist methods that study elements of a system in isolation, the Gladstone Center for Systems and Therapeutics investigates systems holistically. It uses cutting edge approaches to understand entire systems involved in complex biology, from a cell to the central nervous system. The center is directed by Steve Finkbeiner, MD, PhD.
The center relies on powerful tools—such as imaging, genomics, and robotics—to observe multiple variables simultaneously and over a given period of time, thus gaining a deeper understanding of how a system functions, and how its individual elements interact and work together dynamically. To analyze the very large datasets generated by these tools, the center also develops sophisticated mathematical and computational approaches, including deep learning, a form of artificial intelligence.
Supported by Gladstone’s business development office, the center actively collaborates with pharmaceutical companies (Lilly, Merck, etc.), technology companies like Google, and organizations such as the ALS Association and the Michael J. Fox Foundation. It also receives critical support from philanthropic partners. These partnerships allow the center to diligently leverage its discoveries and technologies in ways that can ultimately help patients. As a result, it relies on the tremendous synergy between basic science and translational efforts to develop potential therapies for neurodegenerative diseases, gut disorders, and certain cancers.
Center for Translational Advancement
The Gladstone Center for Translational Advancement was created in 2017 to find unforeseen uses for existing drugs to treat unsolved diseases. Drug repurposing is a powerful approach that drastically lowers the cost and shortens the timeline of drug development. Using FDA-approved drugs, which have already passed safety tests, can help bring treatments to patients more quickly.
Headed by Senior Investigator Yadong Huang, MD, PhD, the center provides crucial resources to develop repurposed drugs that target diseases of the central nervous system, the heart, and the immune system. The center aims to accelerate the conversion of basic research findings into efficient clinical candidates and, ultimately, medical applications.
The center includes three major components:
- Build a drug repositioning database of up to 15,000 compounds using human cells derived from induced pluripotent stem cells (iPSCs). The result will be a public database that outlines how each drug affects healthy and diseased human genes.
- Establish infrastructure to test repurposed drugs in cell culture and animal models for potency, pharmacokinetic (PK), and pharmacodynamic (PD) studies. This will be implemented along with Gladstone Senior Investigator Sheng Ding, PhD, who is also Dean of the School of Pharmaceutical Sciences at the Tsinghua University in Beijing, which has well-established drug discovery and translational platforms.
- Promote human clinical trials of repurposed drugs, in collaboration with medical centers (like UC San Francisco) and pharmaceutical companies in the US and abroad.
Hellman Family Foundation Alzheimer's Research Program
Thanks to a 2011 gift of $1 million from the Hellman Family Foundation, Gladstone launched the Hellman Family Foundation Alzheimer’s Research Program to help spur the development of medications for this devastating illness. Headed by Gladstone Senior Investigator Steve Finkbeiner, MD, PhD, the Program encourages industry interest in creating drugs for the millions around the world with Alzheimer’s disease. The Hellman Family Foundation Alzheimer’s Research Program at Gladstone, which operates in collaboration with the Memory and Aging Center at the University of California, San Francisco (UCSF), leverages infrastructure, resources and research from Gladstone’s existing Taube-Koret Center for Huntington’s Disease Research.
The Program plays a vital role in addressing what is known as the valley of death among those in the biomedical industry. This is the barren territory that few traverse successfully, as many research institutions fail to move a promising biomedical discovery through all the rigorous tests required before a drug company wants to transform the discovery into a pharmaceutical product to help patients. To help Gladstone discoveries successfully cross through the valley of death, the Hellman Family Foundation Alzheimer’s Research Program subsidizes the myriad of early-stage, de-risking tests necessary to make a drug candidate more attractive to pharmaceutical-industry partners, such as tests that reveal at what concentrations a drug stops being therapeutic and instead becomes toxic. Further, the program’s partnership with UCSF’s Memory and Aging Center improves our capacity to do clinical trials.
Gladstone founded the Roddenberry Center for Stem Cell Biology and Medicine in 2011 with an unprecedented $5M gift from the Roddenberry Foundation. Deepak Srivastava, MD, leads the Center, which was set up to honor Star Trek creator Gene Roddenberry. In part, the Center builds on pioneering work done by Gladstone Senior Investigator Shinya Yamanaka, MD, PhD—who currently divides his time between Gladstone and Kyoto University’s Center for iPS Cell Research and Application (CiRA). Dr. Yamanaka’s 2006 discovery of induced pluripotent stem cells, or iPS cells, has altered the fields of cell biology and stem cell research—opening promising new prospects for both personalized and regenerative medicine. The Center, which collaborates with CiRA, is creating human, iPS-based disease models needed to accelerate drug development for a host of devastating for cardiovascular, viral and neurological illnesses.
Scientists working at the Center focus on applying the pioneering the principles of stem cell biology for the advancement of human health. The Center provides them with resources for both blue-sky and de-risking work: blue-sky research follows up on promising but uncertain scientific leads; while de-risking research is necessary to move a promising biomedical discovery through all the rigorous tests required for clinical applications.
Taube/Koret Center for Huntington's Disease Research
In 2009, Gladstone joined forces with Taube Philanthropies and the Koret Foundation to found the Taube/Koret Center for Huntington's Disease Research. The Center focuses on new solutions for overcoming this crippling neurodegenerative disorder, which robs patients of their independence by causing things such as short-term memory loss, involuntary movements of the head and trouble with swallowing. Eventually, fatalities occur from complications such as choking or heart failure. No approved drugs exist to even slow the progression of this relentless disorder.
Gladstone’s Taube/Koret Center plays a vital role in decreasing such human suffering by addressing what is known in the biomedical industry as the valley of death. This is the barren territory that few traverse successfully, as many research institutions fail to move a promising biomedical discovery through all the rigorous tests required before a drug company wants to transform the discovery into a pharmaceutical product to help patients. To help Gladstone discoveries successfully cross through the valley, the Taube/Koret Center subsidizes the myriad of early-stage, de-risking tests necessary to make a drug candidate more attractive to pharmaceutical-industry partners, such as tests that reveal at what concentrations a therapeutic compound becomes efficacious—or toxic.
The Center is also an example of how Gladstone leverages donations for maximum benefit to patients. Using the inaugural $3.6M gift from the Koret Foundation and Taube Philanthropies, Gladstone has since brought in $22M in additional donations. This pattern of leverage can double the value of a gift and ultimately lead to more value to patients and families struck by devastating diseases such as Huntington’s.