Draft:Melissa E. Murray (neuropathologist)

Introduction
Dr. Melissa E. Murray (born 1980) is an American translational neuropathologist and Professor of Neuroscience at Mayo Clinic Florida. She directs the Translational Neuropathology laboratory and is co-director of the Mayo Clinic brain bank. She specializes in the study of neurodegeneration, particularly relating to Alzheimer’s disease and related dementias with an emphasis on young-onset Alzheimer’s disease. Her expertise in digital pathology and discovery of neuropathologic subtypes of Alzheimer’s disease has made her a pioneer in the field of neurodegenerative research. Dr. Murray has led and/or contributed to numerous high-impact publications, which has earned her the recognition of the 2022 Investigator of the Year award at Mayo Clinic Florida, among other honors. .

Early life and education
Dr. Murray was born in Florida and raised in both Florida and Pennsylvania. She moved between the states throughout her life, having attended 10 schools before college. She received her Bachelor of Science in Biology with University Honors from the University of North Florida. She completed her Ph.D. at Mayo Clinic College of Medicine in 2010, where she studied the age effects on white matter through an integration of neuropathology, neuroimaging, and behavioral neurology. Her mentorship under Dr. Dennis W. Dickson and Dr. Clifford R. Jack, Jr. enabled Dr. Murray’s dissertation work to lay the foundation for her future research, which provided her a deeper understanding of the aging brain outside the context of neurodegeneration.

Career
After completing her Ph.D., Dr. Murray began her postdoctoral fellowship at Mayo Clinic with a focus on neuropathology, neuroimaging, and genetics. She quickly became an indispensable member of the Department of Neuroscience for her expertise in digital pathology, where she was promoted to Assistant Professor of Neuroscience in 2013.

Dr. Murray has been exceptionally productive in research, with more than 250 current peer-reviewed publications to her name. She has contributed to review articles, book chapters, editorials, and commentaries.

Dr. Murray’s research has utilized digital pathology to quantify disease severity and brain health in Alzheimer’s disease and related dementias. As an early adopter of the technology, she worked to develop and advance the use of digital pathology as a tool for clinicopathologic research. She has used this technique to uncover distinct patterns in the topographic distribution of neuropathologic lesions underlying clinical heterogeneity

In addition to her research, Dr. Murray is committed to mentoring the next generation of scientists and clinicians. She has mentored many young scientists and clinicians, including undergraduate students, post baccalaureate fellows, medical students, postdoctoral fellows, and clinical fellows. Her predoctoral mentees have successfully gone on to medical school and graduate school, followed by strong careers, and her postdoctoral mentees continue to do well, finding independent careers in industry and academia.

Research
Dr. Murray’s research has made significant contributions to the field of Alzheimer’s disease. One of her most notable papers includes a landmark study published in The Lancet Neurology (2011), where she designed an algorithm to subtype Alzheimer’s disease based on topographic distribution of tangles, leading to the uncovering of neuropathologic influence on syndromic heterogeneity. This study demonstrates Dr. Murray’s ongoing influence on an entire field dedicated to the study of atypical (non-amnestic) Alzheimer’s disease.

In another study published in Brain: A Journal of Neurology (2015), Dr. Murray demonstrated how research-based clinical cutpoints of amyloid-PET imaging corresponded to underlying neuropathology. This study cemented Dr. Murray’s distinct research niche that utilizes a quantitative approach to uncover neuropathologic underpinnings of biomarker changes. The paper also underscored the contribution of tangle pathology over amyloid-β pathology to cognitive decline. Dr. Murray received the Alzheimer’s Association de Leon Prize in Neuroimaging New Investigator of 2016 award recognizing her for her work and its impact on the field.

To further the field’s understanding of hippocampal vulnerability in Alzheimer’s disease, Dr. Murray’s team published a study in in Nature Communications (2021), where they utilized digital pathology as a deep phenotyping approach to reveal novel protein-coding genes implicated in selective vulnerability observed in Alzheimer’s disease. This study highlights her team’s commitment to a holistic approach to understanding Alzheimer’s disease that encompasses both life science and applied sciences in her collaborative effort to bring machine learning approaches to aid in gene prioritization efforts.

Finally, the paper "Global neuropathologic severity of Alzheimer’s disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels" published in the journal Molecular Neurodegeneration in 2022, explores the relationship between plasma phosphorylated tau (p-tau) levels and Alzheimer's disease biomarker changes. The study found that global neuropathologic scales of tau and amyloid-β, as well as the vulnerability of the locus coeruleus, were associated with plasma p-tau levels. The paper theorized that higher soluble plasma p-tau levels may be the result of an intersection between insoluble deposits of amyloid-β and tau accumulation in the brain and may be associated with locus coeruleus degeneration.

Overall, Dr. Murray’s work has made significant contributions to the understanding of Alzheimer’s disease and has been widely cited and recognized by the scientific community.

Honors and awards
Dr. Murray has received several honors and awards throughout her career. In 2012, she was awarded the Robert Terry Award for Best Paper in Neurodegenerative Diseases by the American Association of Neuropathologists for her work on identifying genetic determinants of glial tau pathology in Progressive Supranuclear Palsy. The following year, Dr. Murray was also awarded the Jacksonville Business Journal Health Care Hero award. In 2014, Dr. Murray competed and won funding as one of the top 5 early career investigators in Alzheimer's disease research by the Charleston Conference on Alzheimer's disease. That same year, she was awarded the International Franz Nissl Young Investigator in Neuropathology by the International Society of Neuropathology, as well as the Jacksonville Business Journal's "40 under 40" award. In 2016, Dr. Murray received the Alzheimer's Association de Leon Prize in Neuroimaging award and was named New Investigator of 2016. She was also recognized as one of "The Power List" by The Pathologist. In 2020, Dr. Murray was named a recipient of Clarivate's Web of Science Highly Cited Researcher designation. Most recently, she was awarded the Mayo Clinic Florida Investigator of the Year in 2022. These awards and recognitions attest to Dr. Murray's significant contributions to the field of neuroscience and her dedication to advancing research in neurodegenerative diseases.

Service
Dr. Murray is very active in peer review, serving as a reviewer for 39 journals covering the span of her expertise. These include high-impact journals such as The Lancet Neurology, Acta Neuropathologica, Nature Medicine, and Alzheimer’s & Dementia. She also contributes as an active reviewer for the National Institute of Health (NIH) study sections, as well as several national and international agencies.

Dr. Murray is an active member of various professional organizations at the national level. She is a member of the Human Amyloid Imaging meeting and has been an abstract reviewer for the Human Amyloid Imaging Conference since 2014. In addition, she serves as a program committee advisor for the conference since 2016. She is also a member of the International Society to Advance Alzheimer Research and Treatment, and an abstract reviewer for the Alzheimer’s Association International Conference since 2015. Dr. Murray is a member of several professional interest areas within the Alzheimer’s Association, including the Neuroimaging Professional Interest Area, the Atypical Alzheimer’s Disease and Associated Syndromes Professional Interest Area, and served as an executive committee member of the latter from 2014 to 2021. In 2016, she was appointed as the chair of the Atypical Alzheimer’s Disease and Associated Syndromes Professional Interest Area, and later served as the immediate past chair of the same group from 2019 to 2021. Additionally, she is a member of the American Academy of Neurology and has been an abstract reviewer for its annual meeting since 2019. Finally, she is a member of the Society for Neuroscience and the Digital Pathology Association.

Dr. Murray has served in various professional service capacities. She has served on several committees and working groups of national and international organizations in her area of expertise. At the federal level, she has served as the Co-Chair of the National Institute on Aging Alzheimer's Disease Research Center Digital Pathology Working Group since 2019, and as a member of the National Institute on Aging Alzheimer's Disease Research Center Biospecimens Best Practices Guideline Task Force in 2020. She was also a member of the National Institutes of Health Vascular Contributions to Cognitive Impairment and Dementia (VCID) Session Committee for the Alzheimer’s Disease-Related Dementias (ADRD) Summit in 2022, and a member of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Neuropathology Resource Allocation Review Committee in 2022.

At the foundation level, Dr. Murray served as co-organizer of the Southeastern Neurodegenerative Disease conference (SENDCon) since 2019. She has also been a member of the Alzheimer's Association Workgroup for Appropriate Use Criteria of Amyloid PET since 2020. She served on the advisory board of the Charleston Conference on Alzheimer’s Disease in 2021, and Co-Chair of Chan Zuckerberg Initiative’s Modernizing Neuropathology working group since 2021. She is also a member of the Alzheimer's Association International Conference (AAIC) Scientific Program Committee (SPC) since 2022.

At the international level, Dr. Murray was appointed as a PCA International Expert Panel Member for the UK Medical Research Council in 2022.

Funding
Dr. Murray has been exceptionally successful in securing extramural funding for her research. Although a rocky start as most young investigators face, she has developed an independent program with continuous funding from intramural and extramural grant programs since 2012. Her work has been supported by numerous organizations, including the National Institute on Aging, Alzheimer’s Association, Chan Zuckerberg Initiative, and Rainwater Charitable Foundation.

As of now, she is the principal investigator (PI) on six extramurally funded grants, with a total direct amount awarded of ~$9,000,000. Her research has been supported by the National Institute on Aging (NIA) through multiple grants, including her first NIA R01 grant (AG054449) that recently ended. In addition, Dr. Murray is also an MPI on two R01 grants (AG073282 and AG075802) and two U01 grants (AG057195 and AG069701). These grants cover a range of research topics in Alzheimer’s disease including neuropathologic subtypes, investigating regional and cellular vulnerabilities to tau pathology in young-onset Alzheimer’s disease, and tau PET/CT for early detection of pathology. The grants run from 2017 to 2026, and Dr. Murray's leadership and expertise are expected to significantly contribute to the field of Alzheimer's disease research through these projects.