New 2020 Publications

2020 has already seen six new SRF-supported papers – including validation of a key tactic to prevent mitochondrial aging by our MitoSENS team, and an in-depth review coauthored by SRF, Underdog Pharmaceuticals and professor W. Gray Jerome on the major LysoSENS target 7-ketocholesterol.

Read the MitoSENS and LysoSENS papers for free at PubMed Central:

… or visit our Publications Library to see more of our recent work!

Revel Pharmaceuticals Launched

Glucosepane crosslink breaker research graduates from top Yale lab into the biotech world

Kizoo Technology Capital leads seed round financing at Revel Pharmaceuticals

SAN FRANCISCO/NEW HAVEN/BERLIN, Jan. 21, 2020 — For the past 10 years, Yale Professors David Spiegel and Jason Crawford have been working on tools to enable the development of glucosepane-cleaving drugs. Kizoo Technology Capital investors say now is the time to advance this groundbreaking research toward the clinic and are leading funding of a new company, Revel Pharmaceuticals Inc., founded by Drs. David Spiegel, Jason Crawford, and Aaron Cravens.

Kizoo leads the seed financing round at Revel, with Oculus co-founder Michael Antonov participating. SENS Research Foundation provided funding to the YaleGlycoSENS group for several years.

Glucosepane Biology in relation to Aging and Disease

The long-lived collagen proteins that give structure to our arteries, skin, and other tissues are continuously exposed to blood sugar and other highly reactive molecules necessary for life. Occasionally, these sugar molecules will bind to collagen and form toxic crosslinks that alter the physical properties of tissues and cause inflammation. As a result, tissues slowly stiffen with aging, leading to rising systolic blood pressure, skin aging, kidney damage, and increased risk of stroke and other damage to the brain.

Perhaps the most important of these Advanced Glycation End-products (AGE) crosslinks is a molecule called glucosepane. Revel is developing therapeutics that can cleave glucosepane crosslinks thus maintaining and restoring the elasticity of blood vessels, skin, and other tissues, and preventing the terrible effects of their age-related stiffening.

Revel opens a new category in the SENS repair approach to aging

The Yale group’s first major milestone – the first complete synthesis of glucosepane – was highly recognized when published in Science. Since then progress has been rapid, with development of glucosepane binding antibodies and discovery of therapeutic enzyme candidates capable of breaking up glucosepane crosslinks. Revel will build upon this progress by advancing the first GlycoSENS therapeutics into the clinic.

This is truly a first. We are proud to help Revel open an entirely new category in repairing a significant damage of aging – crosslinking of collagen. Glucosepane crosslinks may cause not only wrinkles on your face but also lead to age-related rising blood pressure and possibly stroke.” says Frank Schueler, Managing Director of Kizoo Technology Capital.

David Spiegel, MD, PhD, Professor of Chemistry at Yale University and Revel founder says: “We are delighted to join Kizoo in building a world-class team to advance crosslink-breaking therapeutics into the clinic. These first-in-class agents have enormous potential to help patients suffering from a wide range of diseases.

Collagen is the infrastructure of our bodies – in every tissue, supporting cellular function and health – but with aging, this critical molecular infrastructure accumulates damage. By clearing out this damage, we can restore tissue function and repair the body. Revel is one of only a few companies taking a repair-centric approach to treat diseases of aging and one day our AGE-cleaving therapeutics will undo this damage at the molecular level.” says Aaron Cravens, co-Founder of Revel Pharmaceuticals.

About Revel

Revel Pharmaceuticals is a biotechnology company located in San Francisco, CA. with a technology platform based on the work of Yale Professors David Spiegel and Jason Crawford. We are commercializing therapeutic designer enzymes to degrade molecular damage that accumulates with aging. By addressing one of the hallmarks of aging, Revel is strategically positioned to develop therapeutics for multiple diseases of aging including osteoarthritis, kidney disease, cardiovascular disease, skin aging, and complications of diabetes.

See www.revelpharmaceuticals.com

About Kizoo

Kizoo provides mentoring and seed and early-stage financing with a focus on rejuvenation biotechnology. Having been entrepreneurs, VCs, and mentors in both high-growth tech and biotech companies for many years, with multiple exits and massive value created for the founders, Kizoo now brings this experience to the emerging field of rejuvenation biotech – a young industry that will eventually become much bigger than today’s largest technology markets.

As part of the Forever Healthy Group, Kizoo directly supports the creation of startups turning research on the root causes of aging into therapies and services for human application. Investments include AgeX, FoxBio, Turn.bio, Elevian, Oisin Biotechnologies, Underdog Pharmaceuticals, MAIA Biotechnology, and others.

Forever Healthy’s other initiatives include the evaluation of new rejuvenation therapies, evidence-based curation of the world’s cutting-edge medical knowledge, funding research projects on the root causes of aging, and hosting the annual Undoing Aging Conference.

For more information, please visit kizoo.com and forever-healthy.org

Contact:
Frank Schueler
Managing Director, Kizoo Technology Capital GmbH
Amalienbadstr. 41, 76227 Karlsruhe
[email protected], +49 721 51600

Underdog Pharmaceuticals Launched

Novel therapeutic approach to cardiovascular disease from SENS Research Foundation flagship research program graduates from laboratory to the biotech world

Kizoo Technology Capital leads seed round financing at Underdog Pharmaceuticals

SRF announces leadership appointments

MOUNTAIN VIEW, Calif., Nov. 14, 2019 (GLOBE NEWSWIRE) — Underdog Pharmaceuticals, Inc. (Underdog), and SENS Research Foundation (SRF) today announced the launch of Underdog and the completion of its seed round, providing $3.95 million to promote Underdog’s development of disease-modifying treatments for atherosclerosis and other age-related diseases. SRF also announced two senior appointments.

The Underdog round is led by Michael Greve’s Kizoo Technology Capital, part of the Forever Healthy Group and one of the premier organizations focusing on accelerating rejuvenation biotechnologies. It also includes Oculus co-founder Michael Antonov through Tubus, LLC, and financier Harald McPike through Chambray Worldwide, Ltd.

Underdog was built from an SRF flagship program that has driven two years of applied development designed to explore and repair the underlying causes of cardiovascular disease. Its co-founders are Matthew O’Connor, Ph.D. and Michael Kope, formerly the V.P. of Research and the founding CEO, respectively, of SRF.

“We’ve taken a well-known and extremely safe compound,” said O’Connor, “and have created novel derivatives that can specifically target the toxic biomolecule that drives the development of atherosclerosis, the cause of most heart attacks and strokes.”

Underdog’s research has combined computational and synthetic chemistry programs to create custom-engineered cyclodextrins (polysaccharides with known industrial and pharmaceutical excipient uses) to capture, and remove from cells, oxidized cholesterol derivatives such as 7-ketocholesterol, which are broadly toxic molecules with no known biological function. “Underdog will take a classic pharmaceutical approach and use it to attack the root causes of cardiovascular disease,” said Kope. “If we’re successful, we won’t just be ameliorating the disease, but reversing it.”

Underdog’s advisors include world-renowned cyclodextrin expert Dr. Lajos Szente. “This elegant approach has the potential to be truly revolutionary,” Szente said. “I’m delighted to be working with them on this important advancement in the field.”

“I came to Aubrey de Grey years ago so that we could work together to accelerate the availability of human rejuvenation therapies,” said Greve. “I am proud to help SRF grow a flagship research program into a genuine company and to help unlock the required capital to develop a true rejuvenation therapy. I’m gratified that we’ve done this while continuing to allow for the health and growth of SRF itself, one of our most important engines for the rejuvenation pipeline.”

The agreement between the organizations will provide equity, royalties, and milestones for the future support of SRF programs.

As Underdog spins out, the V.P. of Research position at SRF has been assumed by Prof. Alexandra Stolzing. Stolzing, a long-standing SRF Research Advisory Board member, received her PhD from the Humboldt University in Berlin, was a postdoctoral fellow at Sheffield University, UK, group leader at the Fraunhofer Institute for Cell Therapy and Immunology, Germany, and then Professor for Biogerontological Engineering at Loughborough University, UK. With over 70 peer-reviewed publications, she has participated in several international research consortia in areas including regenerative medicine, cell and gene therapy development, and neurodegenerative diseases. Her industry experience includes startup CSO and VP of Research roles. Said Stolzing, “I’ve always been passionate about translational research in aging, and I’m very excited to join SRF, where I look forward to translating SRF’s basic science projects, initiating new projects, and helping generate the next wave of healthspan spinouts.”

Science and technology investor and longtime SRF board member Jim O’Neill has stepped in to lead the SENS Research Foundation as interim CEO. He will also spearhead the search for the incoming permanent CEO. O’Neill has advised, invested in, and nurtured more than sixty science and technology companies. While running the Thiel Foundation, he co-founded the Thiel Fellowship and helped create deep science fund Breakout Labs. Previously, he helped lead the U.S. Department of Health and Human Services as the principal associate deputy secretary, where he was responsible for overseeing policy and regulations at NIH, FDA, and CDC and led two major reforms of FDA. He supported the creation of the Armed Forces Institute for Regenerative Medicine, served on the steering committee of the Biomedical Advanced Research and Development Authority, and represented the United States on the U.S. delegation to the World Health Assembly. “Over the past decade, Mike and Aubrey built a team of scientists dedicated to damage repair and turned skeptics into advocates along the way,” said O’Neill. “The growing interest in technologies that can reverse aging is proof of their vision and determination. I’m excited to advance SRF’s vision to bring the benefits of such technologies to the public.”

“This is an historic moment for SENS Research Foundation,” said Dr. Aubrey de Grey, co-founder and Chief Science Officer of SRF. “Underdog may well become one of the most significant endeavors in the rejuvenation biotechnology industry, and Mike and Oki are the perfect team to make it a success. And with Jim’s deep experience in investment and policy, and Alex’s brilliance in research and teaching, I’ve no doubt our mission is in good hands. I’m delighted to have their leadership and expertise at SRF.”

About Underdog

Underdog Pharmaceuticals, Inc., is pursuing a mission to treat the underlying causes of age-related disease. The company develops simple and direct interventions targeting toxic forms of cholesterol using rationally designed molecules to provide the first true disease-modifying treatments for age-related diseases such as atherosclerosis, hypercholesterolemia, heart failure, and macular degeneration. Its products are based on novel derivatives of a well-known, safe compound and a new way of looking at cardiovascular disease created through a SENS Research Foundation program. For more information, please visit underdogpharma.com.

About SENS Research Foundation

SENS Research Foundation is a 501(c)(3) nonprofit that works to research, develop and promote comprehensive regenerative medicine solutions for the diseases of aging. SRF supports research projects focused on a damage repair paradigm at universities and institutes around the world with the goal of curing such age-related diseases as heart disease, cancer, and Alzheimer’s disease. SRF educates the public and trains researchers to support a growing regenerative medicine field through advocacy campaigns and educational programs. For more information, please visit sens.org.

About Kizoo

Kizoo provides mentoring and seed and early-stage financing with a focus on rejuvenation biotechnology. Having been entrepreneurs, VCs, and mentors in both high-growth tech and biotech companies for many years, with multiple exits and massive value created for the founders, Kizoo now brings this experience to the emerging field of rejuvenation biotech – a young industry that will eventually become much bigger than today’s largest technology markets.

As part of the Forever Healthy Group, Kizoo directly supports the creation of startups turning research on the root causes of aging into therapies and services for human application. Investments include AgeX, FoxBio, Turn.bio, Elevian, Oisin Biotechnologies, LIfT BioSiences, MAIA Biotechnology, and others. Forever Healthy’s other initiatives include the evaluation of new rejuvenation therapies, evidence-based curation of the world’s cutting-edge medical knowledge, funding research projects on the root causes of aging, and hosting the annual Undoing Aging Conference. For more information, please visit: kizoo.com and forever-healthy.org.

Notice:
This press release is not an offer to sell or a solicitation of an offer to buy securities in any jurisdiction. No securities commission or regulatory authority has approved or disapproved the information contained herein.

Media contacts:
For Underdog: [email protected]
For SRF: [email protected]
For Kizoo: [email protected]

Identification and Targeting of Noncanonical Death Resistant Cells

SENS Research Foundation Research Center

Forever Healthy Foundation Fellowship in Rejuvenation Biotechnology

Principal Investigator: Tesfahun Admasu

When cells age, they lose their proliferative capacity and stop dividing in a phenomenon called senescence. Cellular senescence decreases the regenerative capacity of cells and tissues.

Throughout the aging process senescent cells accumulate and secrete a characteristic set of proteins, called a senescence-associated secretory phenotype (SASP). Although SASPs act as tumor suppressors and recruit immune cells to repair damage, they also mediate the deleterious effects of senescence to cause different pathologies, such as cancer, neurodegenerative diseases and diabetes. Furthermore, SASPs induce senescence in the surrounding cells (secondary senescence), which aggravates the effect.

Small molecules, called senolytics, eliminate senescent cells and reduce certain age-associated disorders.

Project Goals

This project seeks to test the hypothesis that secondary senescent cells are different from primary senescent cells and would therefore need a different set of senolytics to eradicate. In addition, the project will study the role of the different SASP components involved in the spreading of senescence, and test the hypothesis that intervening in SASP signaling could be therapeutically viable.

Job Opportunity: Research Assistant (Immunology)

SENS Research Foundation (SRF) is hiring a Research Assistant for our Research Center (RC) located in Mountain View, CA. SRF is an exciting, cutting edge non-profit dedicated to transforming the way the world researches and treats age-related disease.

We are seeking a Research Assistant in our Senescence Immunology group for a project geared toward developing therapeutic interventions to rejuvenate immune clearance of senescent cells. This project involves working with human blood samples and primary human cells. This is a full-time position.

Qualified candidates will have a BS or MS in the chemical/biological sciences and substantial bench experience. Duties will include mostly bench work in a small team-oriented environment.

Candidates should have experience in WBC purification, culturing primary cells, quantitative real-time PCR, western blot, immunofluorescence, ELISA, micro plate readers, FACS analysis, and data analysis. Candidates with experience in 2nd and 3rd generation lentivirus system are particularly encouraged to apply.

Interested candidates should submit a cover letter and resume to [email protected].

We offer an excellent benefits package including paid vacation and sick leave, fully covered health insurance (inclusive of dependents), an FSA program, and a company matched 401(k) plan, all of which is offered after a 90-day introductory period. SENS Research Foundation is an equal opportunity employer.

The position is available now and will be filled as soon as the qualified candidate is found. Salary is commensurate with job title.

Job Type: Full-time
Salary: $48,000 to $50,000/year

SRF Research Center Immunologist Application Form

UPDATE: This post has been filled.

Immunologist

SENS Research Foundation (SRF) is seeking a full-time researcher for a Scientist position to work at our Research Center located in Mountain View, California. The position is to lead a new intramural research project geared toward performing translational research studying aging as it relates to the immune system, with a possibility of developing a new therapeutic. This is a collaborative effort between SRF and the Campisi Lab at the Buck Institute for Research on Aging, located in Novato, CA. The collaboration allows the researcher to work with two institutions at the forefront of the anti-aging field, and allow for mentorship from experts in the field. The successful applicant will work with, and be guided by, senior researchers at both SRF and the Buck, and as such this position is available to new PhDs as an alternative to doing a Postdoc (or a 2nd postdoc). The position offers the opportunity for upward mobility into a more senior, PI level position. Leading a team at SRF is an exciting career opportunity in a team environment where everyone is dedicated to discovering new treatments for the diseases and disabilities of aging.

Required Experience

  • PhD or equivalent doctoral degree in the chemical/biological sciences
  • Expertise in the innate immune system

Desired Capabilities

  • Independent planning and project design
  • NK cell knowledge or experience
  • Proficient at the bench and with data analysis
  • Management / mentoring experience
  • Comfortable working in a small team environment and with collaborations with other institutions

Compensation

SRF is proud to offer a competitive salary of $65-75,000/yr for this position, which includes paid vacation and sick leave, fully covered health insurance, inclusive of dependents, an FSA program, and a company matched 401(k) plan offered after a 90-day introductory period. SRF is an equal opportunity employer.

Interested candidates should apply by email to Dr. Matthew O’Connor, taking care to include all of the information and documentation listed below.

Applicants moving onto the second phase of the application process will be contacted by email by a SRF representative for an interview.

Application Information

Contact Information:

  • Last Name / Surname
  • First Name / Given Name
  • Email Address
  • Phone Number
  • Full Mailing Address

Academic Information:

  • Graduate Institution
  • Program or Department
  • Graduation Date
  • First available date to begin position

Documents:

Attach documents in PDF, DOC or DOCX format.

  • CV or Resume.  Please limit your CV or resume to a maximum of 2 pages. Highlight any prior laboratory or research experience. A brief 1- or 2-line description of your specific contribution to each research project is particularly helpful. For instance, the statement “created the expression construct that allowed us to determine protein localization” quickly clarifies your role in the project.
  • Cover Letter.  A cover letter describing your knowledge of SRF’s damage repair approach to aging as well as your experience in immunology; please limit your letter to one page.

A Small Molecule Approach to Removal of Toxic Oxysterols as a Treatment For Atherosclerosis

This research program has successfully spun-out into a company! Visit the Underdog Pharmaceuticals, Inc. website for more information on their transformative approach to atherosclerosis.

SENS Research Foundation Research Center

Principal Investigator: Matthew O’Connor
Research TeamAmelia Anderson, Carolyn Barnes, Angielyn Campo, Anne Corwin, Sirish Narayanan

Many diseases of aging are driven in part by the accumulation of “junk inside cells:” stubborn, damaged waste products derived from the metabolic processes particular to specific cell types. The accumulation of these wastes disables the cell type in question and leads to their dysfunction; when, after decades of silent accrual, a critical number of these cells become dysfunctional, diseases of aging characteristic of that tissue erupt. For example, atherosclerotic lesions form when immune cells called macrophages take in 7-ketocholesterol (7-KC) and other damaged cholesterol byproducts in an effort to protect the arterial wall from their toxicity, only to ultimately fall prey to that same toxicity themselves. These macrophages – now dysfunctional “foam cells” – become immobilized in the arterial wall and spew off inflammatory molecules that in turn promote advanced atherosclerosis, heart attack, and stroke. In other organs, the accumulation of damaged molecules inside vulnerable cells drives Alzheimer’s and Parkinson’s diseases, as well as age-related macular degeneration.

Dr. O’Connor’s team have identified a family of small molecules that may be able to selectively remove toxic forms of cholesterol from early foam cells and other cells in the blood. If effective, these small molecules could serve as the basis for a groundbreaking therapy that would prevent and potentially reverse atherosclerosis and, possibly, heart failure.

Research Highlights:

A lead compound was identified following evaluation of data from human blood sample tests in conjunction with computer modeling to predict the likely behavior of rationally-designed molecules. Preliminary testing has indicated performance consistent with enhanced activity relative to the existing family of compounds: specifically, the candidate molecules exhibit selective targeting of toxic cholesterol byproducts, with significantly reduced affinity for native cholesterol. A patent application for this lead compound and others to be derived from it has now been submitted.

The team is now working to refine their original assay with the expectation that it will more accurately reflect the desired activity on toxic and native cholesterol, and also on an entirely different chemical approach to improved molecules derived from the original family. We are also working with a potential contract laboratory to test the absorption, circulation to tissues, and disposal of our lead candidate, and to perform toxicity assays. SRF has recently acquired a new robotic system to run the assay, which our in-house engineer, Anne Corwin, is now working to set up and program; the end result will be an increase in throughput that allows more rapid testing of more molecules.

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