Schick Group
Research Group Genetics and Cellular Engineering
Our focus is on using genetics for pathway investigation and engineering synthetic cellular systems for drug discovery. In particular, we are interested in the capabilities presented by the powerful CRISPR/Cas9 system, both from a target discovery perspective as well as for application in cell engineering for medical therapeutics.
About our Research
Multitudinous aspects of human health and disease are influenced by cell death. On one hand, too little cell death can lead to tumor formation, or can block cancer therapeutics from working properly. We would like to understand these resistance mechanisms so that we can overcome them for the better prevention and treatment of cancer. On the other hand, too much cell death is responsible for degenerative diseases, such as Alzheimer’s disease (AD), diabetes, or in course of infections and aging. Similarly here, we endeavor to learn the mechanism of why cells die due to these diseases and how to prevent it.
We apply the technologies described below for targeting novel pathways with engineered therapeutics.
We use forward genetics to identify novel cell death pathways in somatic cells. The CRISPR toolbox has powerful new toys which we employ to investigate new players in apoptotic and programmed non-apoptotic cell death pathways. To support these efforts we have developed in-house software to rapidly identify significant new proteins that accelerate the usage of CRISPR-based screening in novel applications. Newly discovered members serve as a basis for pharmacological intervention as well as to elucidate control mechanisms in cell physiology.
We have developed a wholistic genetics platform for discovery of novel cell death networks and pharmacologicals using CRISPR knockouts, knockdown (CRISPRi), and overexpression (CRISPRa). Paired with modern -omics techniques, we not only identify linear cell death pathways, but also interrogate larger cell death networks. Together with pharmacological tools, these methods have the potential to reveal combinational therapies for cancer and degenerative diseases.
Extracellular vesicles (EVs), small membrane bound entities of approximately 30-1000nm size, are released by all cell types and contain protein, lipids or ribonucleotides. EVs, and in particular a subclass called exosomes, can cross the blood brain barrier and therefore constitute an exciting new method to deliver small molecules cargoes to the brain.
We use our CRISPR genetic toolkit to identify factors that promote EV production and release. We moreover are performing screens to identify factors enhancing EV uptake. This should allow us to specifically deliver EVs to specific cell types, or transiently express receptors for EVs in target cell types to facilitate uptake.
Group Leader Genetics and Cellular Engineering
Technical Assistant Schick Lab
Doctoral Researcher Schick Lab
Associate Professor, Visiting Scholar Schick Lab
Doctoral Researcher Schick Lab
Our Publications
Peng, H. ; Pfeiffer, S. ; Varynskyi, B. ; Qiu, M. ; Srinark, C. ; Jin, X. ; Zhang, X. ; Williams, K. ; Groveman, B.R. ; Foliaki, S.T. ; Race, B. ; Thomas, T. ; Chen, C. ; Müller, C. ; Kovács, K.J. ; Arzberger, T. ; Momma, S. ; Haigh, C.L. ; Schick, J.A.
Prion-induced ferroptosis is facilitated by RAC3.Yang, Y. ; Peng, H. ; Meng, D. ; Fa, Z. ; Chen, Y. ; Lin, X. ; Schick, J.A. ; Jin, X.
Stress management: How the endoplasmic reticulum mitigates protein misfolding and oxidative stress by the dual role of glutathione peroxidase 8.Peng, H. ; Xin, S. ; Pfeiffer, S. ; Müller, C. ; Merl-Pham, J. ; Hauck, S.M. ; Harter, P.N. ; Spitzer, D. ; Devraj, K. ; Varynskyi, B. ; Arzberger, T. ; Momma, S. ; Schick, J.A.
Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia.Dai, E. ; Chen, X. ; Linkermann, A. ; Jiang, X. ; Kang, R. ; Kagan, V.E. ; Bayir, H. ; Yang, W.S. ; Garcia-Saez, A.J. ; Ioannou, M.S. ; Janowitz, T. ; Ran, Q. ; Gu, W. ; Gan, B. ; Krysko, D.V. ; Zhu, X. ; Wang, J. ; Krautwald, S. ; Toyokuni, S. ; Xie, Y. ; Greten, F.R. ; Yi, Q. ; Schick, J. ; Liu, J. ; Gabrilovich, D.I. ; Zeh, H.J. ; Zhang, D.D. ; Yang, M. ; Iovanna, J.L. ; Kopf, M. ; Adolph, T.E. ; Chi, J.T. ; Li, C. ; Ichijo, H. ; Karin, M. ; Sankaran, V.G. ; Zou, W. ; Galluzzi, L. ; Bush, A.I. ; Li, B. ; Melino, G. ; Baehrecke, E.H. ; Lotze, M.T. ; Klionsky, D.J. ; Stockwell, B.R. ; Kroemer, G. ; Tang, D.
A guideline on the molecular ecosystem regulating ferroptosis.Varynskyi, B. ; Schick, J.A.
Hacking the lipidome: New ferroptosis strategies in cancer therapy.Bauer, A. ; Puglisi, M. ; Nagl, D. ; Schick, J. ; Werner, T. ; Klingl, A. ; El Andari, J. ; Hornung, V. ; Kessler, H. ; Götz, M. ; Grimm, D. ; Brack-Werner, R.
Molecular signature of astrocytes for gene delivery by the synthetic adeno-associated viral vector rAAV9P1.Xin, S. ; Müller, C. ; Pfeiffer, S. ; Kraft, V. ; Merl-Pham, J. ; Bao, X. ; Feederle, R. ; Jin, X. ; Hauck, S.M. ; Schmitt-Kopplin, P. ; Schick, J.
MS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling.