Miranda Orr, PhD

I  am  a  neuroscientist  with  formal  training  in  developmental  neurobiology,  biology  of  aging,  Alzheimer’s disease and translational science. A  primary goal of my research is to understand cellular and molecular processes driving neurodegeneration and cognitive impairment during the prodromal period associated with Alzheimer’s disease and related dementias.  My program utilizes postmortem human brain tissue to develop clinically  relevant  hypothesis  that  I  test  in  transgenic  mouse  models  of  neurodegeneration. Using  this strategy,  my  work  was  the  first  to  identify  a  link  between  tau  pathology  and  cellular  senescence,  the quintessence   of   latent   tissue   degeneration.   Pharmacological   agents   with   age-modifying   properties effectively  cleared  senescent  brain  cells  and  reduced  neurotoxicity  in  transgenic  mice.  Our  publication (Musi N…Orr ME, 2018) trended in the top 15 on PubMed Tracker, and gained attention from the general public, where it was highlighted in Forbes magazine.

I have received funding by the VA and NIH to continue this  area  of investigation, which  has  catapulted  my  independent career, and  ignited  a  new  field  of study. The NIH’s National Advisory Council on Aging recently listed, “Understanding Senescence in Brain Aging and Alzheimer’s” as an Approved Concept. If  selected  as  a  recipient  for  this  program,  my  New  Vision  Investigator  Award  research  proposal  would investigate  molecular  mechanisms  responsible  for  neuronal  senescence.  Prior  to  our  work,  mitotic  cells were  believed  incapable  of  acquiring  a  canonical  senescence  phenotype.  Therefore  our  innovative research  is  propelling  a  dogma  shift  in  neurobiology,  the  biology  of  aging  and  Alzheimer’s  disease research. My leadership in this field is exemplified by my recent invitation to participate in a NIA-sponsored workshop,   Senescence   in   Brain   Aging   and   Alzheimer’s   Disease.   Along   with   fourteen   other   invited scientists, we will discuss the status of the field and its future directions. As an emerging leader in this new field, I am qualified and committed to continue driving biomedical research in cellular senescence and how it impacts brain aging and neurodegenerative diseases.

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