DIAN Trials Unit Research Fellows

Haiyan Liu MD, MSc
2022-

Postdoc Research Associate
DIAN Trials Unit
Knight Alzheimer’s Disease Research Center
Washington University School of Medicine in St. Louis
600 S. Euclid Ave., Campus Box 8111
St. Louis, MO 63110

Email: haiyanliu@wustl.edu
Phone: 314-273-5819
Fax: 314-747-7060

Dr. Haiyan Liu earned her MD. MSc. Degrees in China. She completed four years of physician training in China and rotated in Internal Medicine, Neurology, and Dermatology. She pursued her postdoctoral training at the University of Michigan, studying central nervous system sensitization, synaptic plasticity, and circuit-level interactions in chronic visceral pain. Dr. Liu conducted seven years of biomedical research in CCR at Washington University School of Medicine related to lysosome function and pathways in Cardiovascular disease, Type II Diabetes Mellitus and Alzheimer’s Disease. She then Joined Dr. Lucey and Dr. Bateman’s lab in the Department of Neurology, Washington University School of Medicine. Her work focused on Amyloid β and Tau measurement in human plasma and CSF, and the effect of Sleep-Deprivation on plasma Aβ and Tau dynamics.

Selected publications:
Yan P, Kim KW, Xiao Q, Ma X, Czerniewski LR, Liu H, Rawnsley DR, Yan Y, Randolph GJ, Epelman S, Lee JM, Diwan A. Peripheral monocyte-derived cells counter amyloid plaque pathogenesis in a mouse model of Alzheimer’s disease. J Clin Invest. 2022 Jun 1;132(11):e152565. doi: 10.1172/JCI152565. PMID: 35511433; PMCID: PMC9151689.

Barthélemy NR, Liu H, Lu W, Kotzbauer PT, Bateman RJ, Lucey BP. Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid. Ann Neurol. 2020 May;87(5):700-709. doi: 10.1002/ana.25702. Epub 2020 Feb 27. PMID: 32057125; PMCID: PMC7289061.

Murphy JT*, Liu H*, Ma X, Shaver A, Egan BM, Oh C, Boyko A, Mazer T, Ang S, Khopkar R, Javaheri A, Kumar S, Jiang X, Ory D, Mani K, Matkovich SJ, Kornfeld K, Diwan A. Simple nutrients bypass the requirement for HLH-30 in coupling lysosomal nutrient sensing to survival. PLoS Biol. 2019 May 14;17(5):e3000245. doi: 10.1371/journal.pbio.3000245. PMID: 31086360; PMCID: PMC6516633.

Liu H, Javaheri A, Godar RJ, Murphy J, Ma X, Rohatgi N, Mahadevan J, Hyrc K, Saftig P, Marshall C, McDaniel ML, Remedi MS, Razani B, Urano F, Diwan A. Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway. Autophagy. 2017;13(11):1952-1968. doi: 10.1080/15548627.2017.1368596. Epub 2017 Nov 25. PMID: 28853981; PMCID: PMC5788488.

Xiao Q, Yan P, Ma X, Liu H, Perez R, Zhu A, Gonzales E, Tripoli DL, Czerniewski L, Ballabio A, Cirrito JR, Diwan A, Lee JM. Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing Aβ Generation and Amyloid Plaque Pathogenesis. J Neurosci. 2015 Sep 2;35(35):12137-51. doi: 10.1523/JNEUROSCI.0705-15.2015. PMID: 26338325; PMCID: PMC4556784.

Xiao Q, Yan P, Ma X, Liu H, Perez R, Zhu A, Gonzales E, Burchett JM, Schuler DR, Cirrito JR, Diwan A, Lee JM. Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis. J Neurosci. 2014 Jul 16;34(29):9607-20. doi: 10.1523/JNEUROSCI.3788-13.2014. PMID: 25031402; PMCID: PMC4099542.

Ma X, Liu H, Foyil SR, Godar RJ, Weinheimer CJ, Hill JA, Diwan A. Impaired autophagosome clearance contributes to cardiomyocyte death in ischemia/reperfusion injury. Circulation. 2012 Jun 26;125(25):3170-81. doi: 10.1161/CIRCULATIONAHA.111.041814. Epub 2012 May 16. PMID: 22592897; PMCID: PMC3397471.

Li Y, Zhang X, Liu H, Cao Z, Chen S, Cao B, Liu J. Phosphorylated CaMKII post-synaptic binding to NR2B subunits in the anterior cingulate cortex mediates visceral pain in visceral hypersensitive rats. J Neurochem. 2012 May;121(4):662-71. doi: 10.1111/j.1471-4159.2012.07717.x. Epub 2012 Mar 27. Retraction in: J Neurochem. 2020 Jun;153(5):662-664. PMID: 22380661.

Former DIAN Trials Unit Fellows

Jorge J Llibre-Guerra. MD, MSc
2018-2021

Assistant Medical Director
DIAN Trials Unit
Knight Alzheimer’s Disease Research Center
Washington University School of Medicine in St. Louis
600 S. Euclid Ave., Campus Box 8111
St. Louis, MO 63110

Email: jllibre-guerra@wustl.edu
Phone: 314-273-5439
Fax: 314-747-7060

Jorge Llibre completed his medical training at the Medical University of Havana, followed by residency in neurology at the National Institute of Neurology, where he was Chief Resident. He has received awards from the Ministry of Health, American Academy of Neurology, World Federation of Neurology, and Havana School of Medicine. University College London awarded him a training experience on Global Mental Health. Llibre created and oversaw the Cognitive and Behavior Research Unit at the National Institute of Neurology in order to help meet the needs of the aging population and was tapped to help in the National Strategy for Dementia and Alzheimer Disease. Llibre was funded by the World Federation of Neurology to develop a dementia-training program for health care providers in Cuba. He joined the Global Brain Health Institute at the Memory and Aging Center, UCSF, where received fellowship training in Behavioral Neurology and Global Mental Health. His research focuses on health disparities in dementia, biomarkers, and neuropsychology of Alzheimer’s disease. Recent work focuses on the influence of African Ancestry markers on cognitive decline in AD.

Selected publications:
Llibre-Guerra JJ, Li Y, Allegri RF, Mendez PC, Surace EI, Llibre-Rodriguez JJ, Sosa AL, Aláez-Verson C, Longoria EM, Tellez A, Carrillo-Sánchez K, Flores-Lagunes LL, Sánchez V, Takada LT, Nitrini R, Ferreira-Frota NA, Benevides-Lima J, Lopera F, Ramírez L, Jiménez-Velázquez I, Schenk C, Acosta D, Behrens MI, Doering M, Ziegemeier E, Morris JC, McDade E, Bateman RJ. Dominantly inherited Alzheimer’s disease in Latin America: Genetic heterogeneity and clinical phenotypes. Alzheimers Dement. 2021 Apr;17(4):653-664. PubMed Central PMCID: PMC8140610.

Llibre-Guerra JJ, Li Y, Schindler SE, Gordon BA, Fagan AM, Morris JC, Benzinger TLS, Hassenstab J, Wang G, Allegri R, Berman SB, Chhatwal J, Farlow MR, Holtzman DM, Jucker M, Levin J, Noble JM, Salloway S, Schofield P, Karch C, Fox NC, Xiong C, Bateman RJ, McDade E. Association of Longitudinal Changes in Cerebrospinal Fluid Total Tau and Phosphorylated Tau 181 and Brain Atrophy With Disease Progression in Patients With Alzheimer Disease. JAMA Netw Open. 2019 Dec 2;2(12):e1917126. PubMed Central PMCID: PMC6991202.

McDade E, Llibre-Guerra JJ, Holtzman DM, Morris JC, Bateman RJ. The informed road map to prevention of 3 Alzheimer Disease: A call to arms. Molecular Neurodegeneration. 2021 July; 16.

Yen Ying Lim, PhD
2013-2015

Senior Research Fellow
Florey Institute of Neuroscience and Mental Health
Melbourne, Australia

Email: yen.lim@florey.edu.au

Dr Yen Ying Lim is head of the Cognitive Health and Ageing Outcomes lab at the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia. She is also the primary investigator of the Healthy Brain Project. Her primary research interests are in integrating and translating the effects of genetic, biological, and lifestyle factors on cognitive decline and clinical disease progression in Alzheimer’s disease. She has published 63 research papers and 2 book chapters. She has a sustained track record of winning fellowships including an NHMRC Career Development Fellowship, and an NHMRC/ARC Dementia Research Development Fellowship. She is also actively involved in the development and validation of computerised cognitive tests in the detection of amyloid-related cognitive change in preclinical Alzheimer’s disease, including the International Shopping List Test (ISLT) and the Online Repeated Cognitive Assessment (ORCA) battery.

Selected publications:
Lim YY, Hassenstab J, Goate A, Fagan AM, Benzinger TLS, Cruchaga C, et al. (2018). Effect of BDNF Val66Met on disease markers in dominantly inherited AD. Annals of Neurology, 84(3), 424-435.

Lim YY, Kalinowski P, Pietrzak RH, Laws SM, Villemagne VL, Porter T et al. (2018) Association of β-amyloid and apolipoprotein E ε4 with memory decline in preclinical Alzheimer’s disease. JAMA Neurology, 75(4), 488-494.

Lim YY & Mormino EM. (2017). APOE genotype and early beta-amyloid accumulation in non-demented older adults. Neurology, 89(10), 1028-1034.

Lim YY, Hassenstab J, Cruchaga C, Goate A, Fagan AM, Benzinger TLS et al. (2016). BDNF Val66Met moderates cognitive impairment, neuronal dysfunction and tau in preclinical autosomal dominant Alzheimer’s disease. Brain, 139(Pt 10), 2766-2777.

Lim YY, Laws SM, Villemagne VL, Pietrzak RH, Porter T, Ames D et al. (2016). Aβ-related memory decline in APOE ε4 non-carriers: Implications for early Alzheimer’s disease. Neurology, 86(17), 1635-1642.

Davis C Ryman, MD PhD
2013-2014

Vice President, Clinical Development
Levo Therapeutics
5215 Old Orchard Rd, Ste 450
Skokie, IL 60077-1047

Email: dryman@levotx.com

After working with Dr Bateman on the DIAN OBS study and associated ADAD research projects during research rotations in his final two years of neurology residency, Davis became the first DIAN-TU Clinical Research Fellow from 2013-14. He learned a great deal about design and execution of clinical trials throughout this experience, which he has continued to apply to research in other rare neurological disorders.

From 2014-17 he worked as Medical Director at AbbVie Pharmaceuticals, where among other projects he partnered with C2N Diagnostics to initiate the first clinical trials of an anti-tau monoclonal antibody for treatment of sporadic AD and progressive supranuclear palsy (PSP). In 2017 he became Executive Medical Director at AveXis, one of the first gene therapy companies to achieve clinical success in developing an AAV9 gene therapy for spinal muscular atrophy, the most common genetic cause of infant death. Following acquisition of AveXis by Novartis in 2018, he became Vice President of Clinical Development at Levo Therapeutics, where he is currently working on development of symptomatic and disease-modifying therapies for Prader-Willi syndrome, a currently untreatable orphan disorder linked to loss of function of a paternally imprinted region on chromosome 15.

Selected publications:
Tang M, Ryman D et al (2016) Neurological manifestations of autosomal dominant familial Alzheimer disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS). Lancet Neurology 2016 Dec;15(13):1317-1325.

Wang F, Ryman D et al (2015) Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease. Neurology 2015 Sep 1;85(9):790-8.

Monserrate A, Ryman D et al (2015) Factors associated with the onset and persistence of post-lumbar puncture headache. JAMA Neurology 2015 Mar 1;72(3):325-32.

Ryman D et al (2014) Factors influencing age of onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 2014 Jul 15;83(3):253-60.