Location

Rochester, Minnesota

Contact

Baker.Darren@mayo.edu

SUMMARY

The research interests of Darren J. Baker, M.S., Ph.D., are focused on the involvement of senescent cells in the processes of aging and cancer.

Cellular senescence, a state of irreversible cell cycle arrest that limits the ability of cells to divide, is a potent anti-tumor mechanism that is also a common feature of aged tissue. Instead of simply being resident cells within a tissue, senescent cells promote various age-related phenotypes due to components that they secrete. Studying the role of cellular senescence in vivo, however, has been difficult due to the lack of reliable markers and the inability to selectively manipulate these cells in animals.

Dr. Baker's research team has developed a transgenic mouse model, termed INK-ATTAC, in which p16-expressing senescent cells can be selectively eliminated in an inducible fashion. By using the INK-ATTAC model in combination with an accelerated aging model, Dr. Baker has demonstrated the ability to significantly delay age-related pathologies and phenotypes, including cataract formation, by removing senescent cells.

Focus areas

  • Senescent cells in natural aging. Dr. Baker's team has demonstrated that removal of senescent cells from a prematurely aged mouse model is effective at delaying a variety of phenotypes that are dependent on the acquisition of senescent cells. The team has now extended these studies into the normal aging processes that occur in mice. Senescent cells expressing p16 increase in many aging tissues, but whether they actively promote age-related pathologies was previously unclear. Dr. Baker's research group has now demonstrated that accumulation of these cells drives pathology in many organs and shortens healthy life. Since the team's approach is to interfere with the viability of senescent cells rather than with their formation, the tumor suppressive functions of the senescence program remain fully intact.
  • The role of senescent cells in Alzheimer's disease and related dementias. Alzheimer's disease (AD), which is characterized by the presence of neurofibrillary tangles and amyloid plaques, is the leading cause of dementia in older adults. However, it was previously unclear whether and how these deposits contribute to AD. Dr. Baker has exploited the observation that both neurofibrillary tangles and neuritic components of plaques in patients with AD show strong immunoreactivity to the cyclin-dependent kinase inhibitor p16, but not to other members of the p16 cell cycle regulatory family of proteins. The p16 biomarker also exhibits increased expression in a variety of tissues with age, but not in terminally differentiated neurons. Implementing disease models, Dr. Baker uses the INK-ATTAC transgenic mice to remove p16-expressing cells. His goal is to improve understanding of how p16-expressing cells contribute to AD.

Significance to patient care

If the novel treatment strategy of eliminating p16-expressing cells is effective in preclinical models, it will open an entirely new avenue for exploration in the treatment of AD. Pharmacological agents, called senolytics, have been described that are capable of eliminating senescent cells in the absence of genetic engineering. These agents are now being used to target senescent cells in a variety of age-related human diseases in early-stage clinical trials.

Professional highlights

  • Recipient, Rising Star Award in Neurodegenerative Research, Mahoney Institute for Neurosciences, University of Pennsylvania, 2019
  • Recipient, Glenn Award for Research in Biological Mechanisms of Aging, Glenn Foundation for Medical Research and American Federation for Aging Research, 2012
  • Recipient, Mary and Joseph A. Pignolo, Sr. Award in Aging Research, Institute on Aging, University of Pennsylvania, 2012
  • Leadership in Aging Fellow, Brookdale Foundation, 2011
  • New Scholar in Aging Research, Ellison Medical Foundation, 2011

PUBLICATIONS

See my publications

PROFESSIONAL DETAILS

Administrative Appointment

  1. Senior Associate Consultant II-Research, Department of Pediatric and Adolescent Medicine
  2. Senior Associate Consultant II-Research, Department of Biochemistry and Molecular Biology

Academic Rank

  1. Associate Professor of Biochemistry and Molecular Biology
  2. Associate Professor of Pediatrics

EDUCATION

  1. Ph.D. - Biomedical Sciences Radboud University
  2. MS - Tumor Biology Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic College of Medicine and Science
  3. BS - Biology, minor in Chemistry University of Minnesota, Twin Cities
.
BIO-00027985

Mayo Clinic Footer