Mertens Lab
neural aging laboratory
Mertens Lab
Neural Aging Laboratory
Department of Neurosciences
University of California San Diego
In the Neural Aging Lab, we reprogram human skin cells into brain cells to better understand age-related diseases. We apply both directly induced neurons (iNs) and induced pluripotent stem cell (iPSC) technologies to develop and learn from the next generation of human disease models.
University of University of California
Innsbruck San Diego
OUR RESEARCH
"Patient-derived models for the human brain are both fascinating and useful. Centered around the actual patient, they can teach us about diseases of the brain."
By combining our patient-centric approach with cellular neuroscience techniques and a passion for big data biology, the goal of our lab is to identify the molecular key players of human biological aging to point toward new treatment strategies for neurological age-related neurodegenerative diseases.
Joe Herdy et al. Cell Stem Cell. 2022
Old human neurons can enter a state of post-mitotic senescence, in which neurons secrete proinflamma-tory SASP factors that can trigger brain inflammation late in life, and particularly in Alzheimer's Disease.
Lena Böhnke et al. Cellular Reprogramming. 2022
The small molecule DMH1, a highly selective ALK2-inhibitor, can efficiently replace the recombinant protein Noggin, cutting costs and enhancing reproducability for the direct conversion of adult human fibroblasts into functional iNs.
Larissa Traxler et al. Cell Metabolism. 2022
Alzheimer's Disease patient neurons undergo a Warburg effect-like metabolic shift driven by PKM2. This shift is very similar to what happens in cancer, and an anti-cancer compound rescue signs of Alzheimer.
2021 paper in Cell Stem Cell
Alzheimer's Disease is driven by an age-dependent loss of neuronal cell identity. It is a 'fate-loss' disease and in many ways surprisingly similar to cancer.
OUR TEAM
JEROME MERTENS
Jerome is Associate Professor at the Department of Neurosciences of UCSD, and Adjunct at the Salk Institute in La Jolla, CA. Before he was Assistant Professor at the University of Innsbruck in Austria. His research focus is to better understand the interface between the biology of aging and neurodegeneration. Jerome completed his PhD in the lab of Oliver Brüstle (University of Bonn) and Philipp Koch, and his postdoc in Rusty Gage’s lab. His work has been supported by grants and fellowships, including a K99/R00, a Marie Curie Fellowship, and an ERC Starting Grant.
SILVIA PELUCCHI
Silvia is a postdoctoral fellow in Jerome's lab and is starting her own lab as a PI at the University of Milan soon. Her interest are the investigation of Alzheimer's disease and other age-related neurodegenerative disorders using iNs and fancy microscopy and muli-omic NGS approaches. Before her postdoc in Innsbruck, she obtained her PhD in Pharmacological Experimental and Clinical Sciences at the University of Milan. Silvia enjoys a lot to get lost in the nature by herself, but mostly she loves to share good food and good wine with friends.
Larissa is a postdoc in Jerome's lab, and her focus is on metabolic alterations in Alzheimer’s Disease. Her research has been supported by a L’Oréal Österreich/ÖUK/ÖAW and a Theodor Körner fellowship. Larissa received her BSc in Molecular Medicine from the Medical University of Innsbruck and her MSc in Biomedicine from Lund University in Sweden. She also actively collaborates with Angelo D'Alessandro's lab at UC Denver, and enjoys frequent research stays at the Salk Institute. In her free time, Larissa loves to spend her time outdoors in the mountains, going for hikes or paragliding, and enjoying a good beer.
JOSEPH R. HERDY
Joe is PhD student in the Neuroscience graduate program at UC San Diego and a joint member of Mertens lab and the Gage lab at the Salk Institute. Joe received his BSc from the University of Alabama in Huntsville and his MSc from the University of Kentucky. Joe's research focuses on the induction of neuronal senescence during aging and neurodegenerative disease. Outside of the lab, Joe enjoys hiking, fishing, rock climbing and any other excuse to spend time outdoors.
LUCIA ZHOU-YANG
Lucy is a graduate student in the lab. She earned her BSc in Health Biology and MSc in Biomedicine at Autónoma University Madrid. Her research in Madrid focussed on gene therapy using iPSC lung organoids, and iPSC modeling in Jun Yao's lab at Tsinghua University in Beijing. Lucy is interested in integrating fate reprogramming technologies with 3D cultures, and age-related diseases. She's always happy, smiley, loves socializing, and always open for any kind of group activities.
♪♪ Dale a tu cuerpo alegría Macarena
Que tu cuerpo es pa' darle alegría why cosa buena
Dale a tu cuerpo alegría, Macarena
Hey Macarena!!!!! ♫♫
SOPHIE EICHHORNER
Sophie is a graduate student in the lab, who already did her BSc in Biology and MSc in Molecular Cell and Developmental Biology at the University of Innsbruck. She is especially interested in neuroscience and aging and developed a fascination in metabolic alterations in neurons that fall victim to age-related diseases. In her free time she enjoys horseback riding, reading and the occasional hike.
OLIVER BORGOGNO
Oli is a graduate student in the lab. He received his BSc in Biology and his MSc in Molecular Biology at the University of Innsbruck. His study focuses on the molecular crosstalk between psychiatric disorders, accelerated aging, and Alzheimer’s disease. Therefore, he uses a hybrid approach consisting of a broad variety of different cell-culture techniques coupled with the subsequent bioinformatic analysis. In his free time Oliver loves to boulder in- and outdoor as well as going on trail runs in the mountains. Since he is a nerd, special interests of him are computers and 3D-printers.
As soon as he finishes his Master, Oliver wants to dig deeper into the possibilities Big Data Biology offer with
a particular focus on Neuroscience and Aging.
Lena is a senior graduate student enrolled in the doctoral AGE_REG PhD program. Lena received her BSc in Molecular Medicine from the University of Erlangen-Nuremberg and her MSc in Molecular Sciences from the University of Lübeck in Germany. Before coming to Innsbruck, she joined Jerome for several research stays at the Salk Institute and worked at the drug discovery alliance and development partnership company Evotec. Lena is currently finishing her PhD thesis writing, and did not move with the lab to San Diego (yet).
JESSICA LAGERWALL
Jessica’s passion lies in investigating the underlying mechanisms of disrupted systems that lead to age-related diseases and disorders of the CNS. With a background in neuropsychiatric genetics (MSc in Genetics from Stellenbosch University), she is particularly interested in using an integrated approach to explore the genetic and physiological underpinnings of these diseases. As a South African native, Jessica is still acclimatising to the sub-zero temperatures, but is very happy to have recently joined the Neural Aging team in Innsbruck. She intends to take advantage of the winter and summer sports, Wiener schnitzels and apfelstrudel, and the incredible scenery Innsbruck has to offer!
FLORIAN SCHOEN
Flo was the lab's Manager at the University of Innsbruck. He completed his MSc in the lab and stayed in Austria and moved on to new exciting projects.
ANNA SMALING
Anna is a completed her MSc in the lab. She now works for Oroboros Instruments
DANIELA FRANTAL
Dani was a Research Assistant in the lab, and she just had a new addition to the family and is currently taking a break from work. We hope she will be back soon :)
TIMON STEIN
Timon did his BSc in the lab working with Jessica on the comparison of adult and fetal neuronal models with ontogenetic tools. He is now supporting the lab as a student research assistant.
LAURA WEIGL
Laura completed her BSc in the lab.
ALUMNI
RAVI AGARWAL
Part-time research assistant supporting the lab in San Diego since a long time :)
-> Medical School at UC San Diego
PHILIPP BOUSSARD
MSc student 2020/2021
-> Humanmedizin, Uni Heidelberg
LUKAS KARBACHER
MSc student
-> Research Assistant, Salk Institute
BELLA ROHWEDER
BSc student 2021
JANINA KASPAR
MSc ERASMUS student 2020
-> MSc at University of Heidelberg (Moritz Mall lab)
ALICE SANTAGOSTINO
BSc student 2020
-> MSc at University of Innsbruck
TIM CIESIOLKA
BSc student 2019-2020
-> Roche Diagnostics
STINA LAGERSTRÖM
xxx
MATILDE IRACI
MSc student 2020/2021
ANNA DENGLER
Lab intern 2022
MolZEB University of Innsbruck.
ISABELLA ANGELI
BSc student 2021
FLORA KOGLER
BSc student 2020
-> BSc at University of Innsbruck
LUKAS C. MAASS
BSc student 2019
-> Roche Diagnostics
SANTIAGO ARDILES
Lab intern 2018-2019
-> MSc at Medical University Innsbruck
ALICE FOLTYNOVA
Post-MSc intern 2021/2022 -> Uni Prague, CZ
LORE HELLEMANS
BSc student 2020
LEA NAGELSCHMIED
BSc intern 2021
KATHARINA SCHULER
MSc intern 2022
JULIA-ANNA ULZ
MSc intern 2022
PUBLICATIONS
’Increased Post-Mitotic Senescence in Aged Human Neurons is a Pathological Feature of Alzheimer’s Disease’
J. R. Herdy, L. Traxler, R.K. Agarwal, L. Karbacher, J.C.M. Schlachetzki, L. Boehnke, D. Zangwill, D. Galasko, C.K. Glass, J. Mertens# & F.H. Gage#.
Cell Stem Cell, Dec 2022
‘Chemical Replacement of Noggin with Dorsomorphin Homolog 1 for Cost-Effective Direct Neuronal Conversion’
L. Böhnke, L. Zhou-Yang, S. Pelucchi, F. Kogler, D. Frantal, F. Schön, S. Lagerström, O. Borgogno, J. Baltazar, J.R. Herdy, S. Kittel-Schneider, M. Defrancesco, and J. Mertens#.
Cellular Reprogramming, Jul 2022.
‘Warburg-like metabolic transformation underlies neuronal degeneration in sporadic Alzheimer’s disease’
L. Traxler, J.R. Herdy, D. Stefanoni, S. Eichhorner, S. Pelucchi, A. Szücs, A. Santagostino, Y. Kim, R.K. Agarwal, J.C.M. Schlachetzki, C.K. Glass, J. Lagerwall, D. Galasko, F.H. Gage, A. D’Alessandro, and J. Mertens#. .
Cell Metabolism, Aug 2022.
‘Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients’
J. Mertens#, J.R. Herdy*, L. Traxler*, S.T. Schafer, J.C.M. Schlachetzki, L. Böhnke, D.A. Reid, H. Lee, D. Zangwill,
D.P. Fernandes, R.K. Agarwal, R. Lucciola, L. Zhou-Yang, L. Karbacher, F. Edenhofer, S. Stern, S. Horvath, A.C.M. Paquola,
C.K. Glass, S.H. Yuan, M. Ku, A. Szücs, L.S.B. Goldstein, D. Galasko, and F.H. Gage#
Cell Stem Cell, Apr 2021
'Metabolism navigates neural cell fate in development, aging and neurodegeneration'
L. Traxler, J. Lagerwall, S. Eichhorner, D. Stefanoni, A. D'Alessandro, and J. Mertens
Disease Models and Mechanisms, 2021
'Improved Method for Efficient Generation of Functional Neurons from Murine Neural Progenitor Cells'
A. Soni, D. Klütsch, X. Hu, J. Houtman, N. Rund, A. McCloskey, J. Mertens, S. T. Schafer, H. Amin, T. Toda
Cells, 2021
'Direct Conversion of Human Fibroblasts to Induced Neurons'
L. Zhou-Yang, S. Eichhorner, L. Karbacher, L. Böhnke, L. Traxler, and J. Mertens
Neural Reprogramming: Methods and Protocols, 2021
'One Big Step to a Neuron, Two Small Steps for miRNAs’
J. R. Herdy, L. Karbacher and J. Mertens#.
Cell Stem Cell, Jan 2021
'When function follows form: Nuclear compartment structure and the T epigenetic landscape of the aging neuron’
J.C.M. Schlachetzki, T. Toda# and J. Mertens#.
Experimental Gerontology, Feb 2020
'Next-generation disease modeling with direct conversion: a new path to old neurons’
L. Traxler, F. Edenhofer, and J. Mertens.
FEBS letters, Dec 2019
‘Take the shortcut–direct conversion of somatic cells into induced neural stem cells and their biomedical applications’
A. Erharter, S. Rizzi, J. Mertens, and F. Edenhofer.
FEBS letters, Dec 2019
‘Chemical modulation of transcriptionally enriched signaling pathways to optimize the conversion of fibroblasts into neurons’
J. R. Herdy, S.T. Schafer, Y. Kim, Z. Ansari, D. Zangwill, M. Ku, A.C.M. Paquola, H. Lee, J. Mertens#, and F.H. Gage#.
eLife, May 2019
‘Human neurons to model aging: A dish best served old‘
L. Böhnke, L. Traxler, J. R. Herdy, and J. Mertens.
Drug Discovery Today: Disease Models, Feb 2019
‘Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons‘
S.T. Schafer, A.C.M. Paquola, S. Stern, D. Gosselin, M. Ku, M. Pena, T.J.M. Kuret, M. Liyanage, A.A. Mansour, B.N. Jaeger, M.C. Marchetto, C.K. Glass, J. Mertens, and F.H. Gage.
Nature Neuroscience, Jan 2019
‘Aging in a dish: iPSC-derived and directly induced neurons for studying brain aging and age-related neurodegenerative diseases'
J. Mertens, D. Reid, S. Lau, Y. Kim, and F. H. Gage.
Annual Reviews Genetics , Sep 2018
‘Mitochondrial aging defects emerge in directly reprogrammed human neurons due to their metabolic profile ‘
Y. Kim, X. Zheng, Z. Ansari, M.C. Bunnell, J.R. Herdy, L. Traxler, H. Lee, A.C.M. Paquola, C. Blithikioti, M. Ku, J.C.M. Schlachetzki, J. Winkler, F. Edenhofer, C.K. Glass, A.A. Paucar, B.N. Jaeger, S. Pham, L. Boyer, B.C. Campbell, T. Hunter, J. Mertens#, F.H. Gage#.
Cell Reports, May 2018