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Ramon Velazquez

Assistant Professor
Post Doctoral Scholars, TEMPE Campus, Mailcode 7601
Assistant Professor
Faculty, TEMPE Campus, Mailcode 7601
Assistant Professor
Faculty, TEMPE Campus, Mailcode 7601
Biography: 

Click link to view laboratory website: https://velazquezlab-asu.github.io/index.html

Ramon Velazquez is an assistant professor in the School of Life Sciences and with the Neurodegenerative Disease Research Center at the Biodesign Institute - Arizona State University. His research interests include identifying novel therapeutic targets for neurodegenerative disorders such as Alzheimer’s disease (AD) and Down Syndrome (DS). In particular, he focuses on early molecular events that trigger the progression of these diseases. He is also interested in drug discovery and dietary supplementation of B-like vitamins as a way to prevent disease progression. Velazquez received his doctoral degree at Cornell University and worked in the laboratory of Dr. Barbara Strupp. Velazquez was funded by the National Science Foundation (NSF) Pre-Doctoral fellowship as a graduate student and completed his postdoctoral training in molecular biology and neuroscience at ASU, where he was independently funded by the Alzheimer’s Association and via a NSF postdoctoral fellowship. Velazquez’s ultimate goal is to progress science while consecutively helping those who suffer from insidious neurodegenerative diseases.

Education: 
  • Postdoctoral Fellow. ASU NDRC (2014-2019)    
  • Ph.D. Cornell University, Ithaca NY (Aug. 2008- Aug 2014)
  • B.A. California State University, Long Beach (May 2002- May 2007)

            

Research Interests: 

As a neuroscientist, I have been mainly interested in deciphering the early molecular events that contribute to the pathogenesis of various neurodevelopmental and neurodegenerative diseases. In particular, I am interested in identifying new therapeutic targets for discovery of drugs that can ameliorate disease progression.  Our lab uses a combination of post mortem human brain tissue in addition to various lines of animal models of Down Syndrome (DS) and Alzheimer's Disease (AD) to test our hypotheses. I strongly believe that in order to progress outcomes within research, collaborations are key. Sharing knowledge through publications, mentorship, teaching and public seminars have been key to furthering my scientific career. My ultimate goal is to make a large impact by both progressing science and consecutively helping those who suffer from insidious diseases.

Research Group: 

Given that the elderly is the fastest growing population in our society and that age is the single most important risk factor for Alzheimer’s disease (AD), there is an urgent need to understand the mechanisms contributing to AD pathology. Doing so, we will be able to develop strategies by which we can prevent the incidence of AD, as well as help those that are currently in advanced stages of this disease. One of the most fruitful approaches for studying neurodegenerative diseases stems from utilizing a multidisciplinary strategy. My graduate and early postdoctoral studies have shaped me into a well-rounded neuroscientist with this type of multidisciplinary approach, as I received extensive training in behavioral neuroscience, animal models of disease, neurobiology and molecular neuroscience. This allows us to ask questions at multiple levels of analysis.  

 

Current projects

The Pim1 kinase as a contributor to the pathological progression of Alzheimer's disease

Pim1, a protein kinase from the proto-oncogene family, emerged in research as it is elevated in various cancers. Within the brain, Pim1 is expressed exclusively in the cortex and hippocampus, two brain regions that are highly vulnerable to AD pathology. We identified Pim1 as being dysregulated in post-mortem brain tissue of patients with in early and late stages of AD compared to age-matched controls. Physiologically, Pim1 phosphorylates and regulates the activity of the proline-rich AKT substrate 40 kDa (PRAS40), which is involved in modulating protein degradation. Pim1 also plays key functions in long-term potentiation and synaptic plasticity, and increased Pim1 activity is linked to seizures and neuronal death. Pim1 is regulated by JAK/STAT, a pathway activated by inflammation. Our recent data illustrates that Pim1 is elevated in CA1 hippocampal neurons of AD patients and our published work shows that pharmacological inhibition of Pim1 rescues AD pathology in 3xTg-AD mice. Notably, 3xTg-AD mice develop amyloid-β plaques and pathological tau, which are the two hallmark pathologies in AD. The current goals of this project is to determine how modulating neuronal Pim1 activity interferes with AD pathology and to dissect the upstream mechanisms linked to Pim1 upregulation. We hypothesize that activation of the JAK/STAT pathway by inflammatory cytokines increases Pim1 activity, which in turn facilitates the development of AD pathology.  

 

Deciphering the early molecular events in Down syndrome that contribute to Alzheimer's Disease progression

Growing evidence indicates that Alzheimer's disease (AD) starts decades before its clinical manifestation and that early clinical interventions are needed to effectively mitigate the progression of AD. However, the initial triggers in the cascade of pathological events leading to AD remain elusive. Virtually 100% of people with Down syndrome (DS) will show brain accumulation of amyloid-β (Aβ) and tau in their fifth decade of life. Despite these data, little is known about the processes linking DS to AD. We postulate that dissecting the molecular mechanisms driving AD pathology in DS patients will lead to a better understanding of the etiology of AD. Previous work indicates that the mammalian target of rapamycin (mTOR) is hyperactive in human and animal models of DS and AD. Further, we and others have shown that hyperactive mTOR signaling facilitates the accumulation of Aβ and tau. Together, these novel and exciting findings may answer a fundamental unresolved question: which event triggers the development of AD neuropathology in DS. The answer to this question will unveil mechanistic changes linked to the etiology of AD. The overall hypothesis of this project is that dysfunctional tuberous sclerosis complex 2 (TSC2), which is a regulator of mTOR, increases it’s activity in DS, which in turn contributes to the development of AD-like neurodegeneration. The results from this work will lead to a better understanding of the mechanism leading to neurodegeneration in DS and AD and will identify new therapeutic targets for these two disorders.

Techniques performed in our laboratory 

  • Development and usage of genetic mouse models of Down syndrome and Alzheimer's Disease (e.g. Ts65Dn, APP/PS1, PS19, APP Knock-in). 
  • Immunohistochemistry                                                                      
  • Western blot assay 
  • Confocal Microscopy
  • MBF unbiased stereology and Neurolucida dendritic spine quantification
  • Genotyping and qPCR
  • Behavioral assessment in mice (Rota Rod, Morris water maze, Radial arm water maze)
  • Automated behavioral assessment in mice using the TSE IntelliCage system

 

Publications: 
  1. Powers B, Velazquez R, Strawderman MS, Ginsberg SD, Muson EJ, Strupp BJ, 2021. Maternal choline supplementation as a potential therapy for Down syndrome: Assessment of effects throughout the lifespan. Front. Aging Neurosci.
  2. Winslow W, McDonough I, Tallino S, Decker A, Vural AS, Velazquez R#, 2021. IntelliCage automated behavioral phenotyping reveals behavior deficits in the 3xTg- AD mouse model of Alzheimer's disease associated with brain weight. Front. Aging NeurosciPMID: 34483889
  3. Dave N, Vural AS, Piras IS, Winslow W, Surendra L, Winstone J, Beach T, Huentelman MJ, Velazquez R#, 2021. Identification of the retinoblastoma binding protein 7 (Rbbp7) as a mediator against tau acetylation and subsequent neuronal loss in Alzheimer’s disease and related tauopathies. Acta NeuropathologicaPMID: 33978814
  4. Mifflin MA, Winslow W, Surendra L, Tallino S, Vural A, Velazquez R, 2021. “Sex differences in the IntelliCage and Morris water maze in the APP/PS1 mouse model of amyloidosis.” Neurobiol. of AgingPMID: 33610962
  5. Velazquez R, Winslow W, Mifflin MA, 2020. “Choline as a prevention for Alzheimer’s Disease.” AgingPMID: 32039834
  6. Velazquez R, Ferreira E, Knowles S, Fux C, Rodin A, Winslow W, Oddo S, 2019. “Life-long choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation.” Aging CellPMID: 31560162
  7. Velazquez R, Meechoovet B, Ow A, Foley C, Shaw A, Smith B, Oddo S, Hulme C, Dunckley T, 2019. “Chronic Dyrk1 Inhibition Delays the Onset of AD-like Pathology in 3xTg-AD Mice”. Mol NeurobiolPMID: 31240602
  8. Velazquez R, Ferreira E, Winslow W, Dave N, Piras I, Naymik M, Huentelman M, Tran A, Caccamo A, Oddo S, 2019. “Maternal choline supplementation ameliorates Alzheimer’s disease pathology by reducing brain homocysteine levels across multiple generations”. Mol. PsychiatryPMID: 30622336
  9. Belfiore R, Rodin A, Ferreira E, Velazquez R, Branca C, Caccamo A, Oddo S, 2018. “Temporal and Regional Progression of Alzheimer’s disease-like pathology in 3xTg-AD mice”. Aging CellPMID: 30488653
  10. Velazquez R, Tran A, Ferreira E, Turner EC, Oddo S, 2018. “Acute Tau knockdown in the hippocampus of adult mice causes learning and memory deficits”. Aging Cell, 17, 1-12. PMID: 29749079
  11. Velazquez R, Tran A, Ishimwe E, Denner L, Dave N, Oddo S, Dineley KT, 2017. “Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer’s disease.” Neurobiol. of Aging 58, 1-13. PMID: 28688899
  12. Powers BP, Kelly CM, Velazquez R, Ash JA, Strawderman MS, Alldred MJ, Ginsberg SD, Mufson EJ, Strupp BJ, 2016. “Maternal choline supplementation in a mouse model of Down syndrome: effects on attention and nucleus basalis/substantia innominata neuron morphology in adult offspring.” Neuroscience 340, 501-514. PMID: 27840230
  13. Velazquez R, Shaw DM, Caccamo A, Oddo S, 2016. “Pim1 inhibition as a novel therapeutic strategy for Alzheimer’s disease.” Mol Neurodegener. 11, 1 – 14. PMID: 27412291
  14. Powers BP*, Velazquez R*, Kelley CM, Ash JA, Strawderman MS, Alldred MJ, Ginsberg SD, Mufson EJ, Strupp BJ, 2016. “Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome.” Brain Struct Funct. 221, 4337-4352. PMID: 26719290
  15. Kelley CM, Ash JA, Powers BP, Velazquez R, Alldred MJ, Ikonomovic MD, Ginsberg SD, Strupp BJ, Mufson EJ, 2016. “Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome.” Curr Alzheimer’s Res. 1, 84-96. PMID: 26391045
  16. Strupp BJ, Powers BE, Velazquez R, Ash JA, Kelley CM, Alldred MJ, Strawderman MS, Caudill MA, Mufson EJ, Ginsberg SD, 2016. “Maternal Choline Supplementation: A Potential Prenatal Treatment for Down Syndrome and Alzheimer's Disease.” Curr Alzheimer’s Res. 13, 97-106. PMID: 26391046
  17. Talboom JS, Velazquez R, Oddo S, 2015. “The mammalian target of rapamycin at the crossroad of aging and Alzheimer’s disease.” Aging and mechanism of diseasePMID: 28721257
  18. Ash JA*, Velazquez R*, Kelley CM, Powers BE, Ginsberg SD, Mufson EJ, Strupp BJ, 2014. “Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.” Neurobiol. Dis 70, 32-42. PMID: 24932939
  19. Kelley CM, Powers BP, Velazquez R, Ash JA, Ginsberg SD, Strupp BJ, Mufson EJ, 2014. “Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice.” J Com Neurol. 522, 1390-1410. PMID: 24178831
  20. Kelley CM, Powers BP, Velazquez R, Ash JA, Ginsberg SD, Strupp BJ, Mufson EJ, 2013. “Sex differences in the cholinergic basal forebrain in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.” Brain Pathol. 24, 33-44. PMID: 23802663
  21. Velazquez R, Ash JA, Powers BE, Kelley CM, Strawderman MS, Luscher ZI, Ginsberg SD, Mufson EJ, Strupp BJ, 2013. “Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome.” Neurobiol. Dis 58, 92-101. PMID: 23643842
Research Activity: 
  1. Developmental Research grant (NIH-Arizona Alzheimer's Consortium); PI Velazquez; Co-PI Huentelman TGen; CO-PI Karr, ASU), (2021-2023)
    PI on a 2-year grant to investigate the role of Neuronal Rbbp7 as a mediator against tau pathology in Alzheimer’s disease and related tauopathies.
  2. Edson Foundation Seed grant (ASU Foundation; PI Velazquez; Collaborators TGen; Huentelman and Pirrotte), (2020-2022)
    PI on a 2-year grant to determine if glyphosate exposure is associated with cognitive aging and Alzheimer’s Disease (AD).
  3. Edson Foundation Seed grant (ASU Foundation; PI Dunckley, Co-PI Velazquez), (2021-2022)
    Co-PI on a 1-year grant to test a novel Dyrk1a inhibitor in the 3xTg-AD mouse model of AD.
  4. Edson Foundation Seed grant (ASU Foundation; PI Mastroeni, Co-PI Velazquez), (2021-2022)
    Co-PI on a 1-year grant to test whether dysfunctional neuronal mitochondria translocate into neighboring glial cells via tunneling nanotubes
  5. IDSA - The Role of Microbe-induced Necroptotic Death in Tauopathy (PI Jacobs; Co-PI Velazquez), (2020-2021)
    Co-PI on a grant to determine mechanisms of cell death in Alzheimer’s disease and related tauopathies.
  6. R01 AG062500 HHS: NIH (PI Velazquez) (2019-2024)
    PI on a grant to identify how the ribosomal protein S6 kinase beta-1 (S6K1) mechanistically links aging and AD.
  7. R01 AG059627 HHS: (NIH PI Velazquez) (2019-2023)
    PI on a grant to identify common mechanisms of neurodegeneration between Down syndrome (DS) and AD.

                                        

Press Releases

https://azpbs.org/horizon/2019/10/asu-researchers-looking-at-common-supplement-to-battle-alzheimers/?fbclid=IwAR0euN5l_CgP4r7pn_l2XDGY6RCinwliK_5XHh5e6Ff2nRfLBtFTEy7G2NY

http://news.cornell.edu/stories/2013/09/more-choline-mom-decreases-down-syndrome-effects

https://asunow.asu.edu/20190108-essential-nutrient-may-help-fight-alzheimers-across-generations

https://www.sciencedaily.com/releases/2019/01/190108084424.htm

https://www.genengnews.com/news/fighting-alzheimers-through-uptake-of-an-essential-nutrient/

 

Fall 2021
Course NumberCourse Title
BIO 495Undergraduate Research
Spring 2021
Course NumberCourse Title
BIO 493Honors Thesis
BIO 495Undergraduate Research
Fall 2020
Course NumberCourse Title
BIO 495Undergraduate Research
Spring 2020
Course NumberCourse Title
BIO 493Honors Thesis
BIO 495Undergraduate Research
Honors / Awards: 

AAAS/Science Program for Excellence in Science (Inducted October 2018)

Biology Travel Award (April 2018)

Society for Neuroscience Trainee Professional Development Award (November 2017)

Alzheimer’s Drug Discovery Foundation Young Investigator Scholar (July 2017)

James Bradford young scholar Award (June 2012)

Neurobehavioral Teratology Society “Best student presentation Award” (June 2012)

Phi Beta Kappa (inducted May 2007)

 

Professional Associations: 

AAS/Science Program for Excellence in Science

Society for Neuroscience 

Phi Beta Kappa

Graduate Faculties / Mentoring History: 

Undergraduate mentorship

1. Zoe I. Lusher – Mentored at Cornell University and was co-authored on one of my publications. She received her B.S. in 2012, an M.D. in 2018 and is now in her medical residency. 

2. An L. Tran - Mentored at Arizona State University as part of the Barrett’s Honor’s college program. She was co- authored on three of my publications. She is now teaching abroad. 

3. Lukith Surendra - Mentored at Arizona State University as part of the Barrett’s Honor’s college program. He will apply for Medical School in Fall of 2019.

4. Marc Mifflin - Mentored at Arizona State University as part of the Barrett’s Honor’s college program. I am a member of the students’ thesis committee (2018-present).

Service: 

Alzheimer's Association Desert Southwest Chapter DJ (2016-present)

Leukemia and Lymphoma Society Phoenix Chapter DJ (2015-present)

Expertise Areas: