Carmen Gerlach Group

The goal of our research is to unravel basic principles and mechanisms underlying the generation, maintenance, and consequences of the diversity within CD8+ T cell responses.

Diversity within the T cell response, T cell memory

CD8 T cells play a crucial role in providing protection against many infections and cancers, but may also contribute to immunopathology in conditions of continuous antigen presence. In recent years it has become clear that T cells are an extremely diverse group of immune cells, and that different T cell subsets have different properties.

T cell subsets differ with respect to their expression of cell surface receptors, their production of inflammatory and cytotoxic mediators, their anatomic localization, and their migratory behavior. As a consequence, not all CD8 T cell subsets play an equal role in the control of infections and tumors, or the pathology associated with inflammatory disorders. What we find particularly interesting is that such diversity exists even among CD8 T cells that recognize the exact same antigen. Using a combination of several state-of-the-art single-cell technologies and experimental model systems, we study how different CD8 T cell subsets arise, what their relationship is, and what mechanisms underlie their specific properties. Our long-term goal is that this knowledge will contribute to improved vaccines and immunotherapies.

• Universal patterns of T cell differentiation across species.
• Clonal aspects of CD8 T cell responses.
• Molecular mechanisms underlying the heterogeneity within T cell responses.
• Exploiting T cell heterogeneity for cancer immunotherapy.

Carmen Gerlach, PhD, Assistant Professor, Principal Investigator.

carmen.gerlach@ki.se

Fascinated by the biology of the human body, I studied Biomedical Sciences at Leiden University in Leiden, the Netherlands (B.Sc. 2003 & M.Sc. 2005). As I wanted to see something of the world at the same time, I participated in an exchange program with the Karolinska Institute in Stockholm, Sweden, and performed an internship in parasitology that included field work in rural northern Ghana. My growing interest in immunology led me to perform my Master thesis in the lab of Rienk Offringa and Kees Melief at the Leiden University Medical Center, and during that time I realized that I wanted to continue my research career in this field. As PhD student in Ton Schumacher’s lab at the Netherlands Cancer Institute in Amsterdam (2005-2011), I got the chance to combine technological development with gaining deeper insights into basic immunological processes. Together with a few colleagues, I developed a cellular barcoding technology that allows in vivo tracking and fate mapping of single naive T cells. Using this technology, I established that while virtually all naive CD8 T cells give rise to both effector and memory cell progeny (Gerlach et al., J.Exp. Med. 2010), individual naive T cells nevertheless mount very distinct immune responses to facilitate robustness of the overall response (Gerlach et al., Science 2013). During my postdoc in Ulrich von Andrian’s lab at Harvard Medical School in Boston, USA (2011-2017), I studied the memory CD8 T cell response in more detail, which led to the delineation of a novel subset, named ‘peripheral memory cells (Tpm)’ that has unique migratory, homeostatic and functional properties (Gerlach et al., Immunity 2016). To gain a better understanding of the computational aspects involved in the analysis of (immune) cells with the current high-dimensional single-cell technologies, I spent 8 months as visiting scholar in Nir Yosef’s lab at the University of California Berkeley in Berkeley, USA (2017). Since November 2017, I am an Assistant Professor at the Karolinska Institute in Stockholm.

Anthonie Zwijnenburg, MD, PhD student.

anthonie.zwijnenburg@ki.se

Before I joined Carmen Gerlach’s lab, I was trained in the Netherlands as a Medical Doctor at the University of Utrecht (B.Sc. 2012 & M.Sc., M.D. 2016). During that time I discovered that my interests lie more towards basic science than clinical medicine. To challenge myself during my Medicine study, I joined the traumatology laboratory at the University Medical Center Utrecht (2011). Halfway through my medical rotations, I decided to take a break from Medicine and to full-time explore my possibilities outside of Europe. That is when I set up a research internship in the lab of Ulrich von Andrian at Harvard Medical School in Boston, USA (2014). There, I met Carmen Gerlach for the first time, as I helped her with studying memory CD8 T cell responses and the delineation of the novel peripheral memory cells (TPM) (Gerlach et al., Immunity 2016). After my year in the USA, I moved back to the Netherlands and finished my medical rotations. For my final scientific internship, I joined Jacco van Rheenen’s lab at the Hubrecht Institute in Utrecht, Netherlands (2016). Here, I worked on human cancer organoids and the spatial analysis of confocal images. After finishing university, I first pursued another life goal by thru-hiking the length of New Zealand on the Te Araroa. Unknowing that Carmen’s and my path would cross again. While walking the last few hundred kilometers I got the message that Carmen was starting her own lab at the Karolinska Institute in Stockholm, and here I am.

Ioana Sandu, PhD, postdoc.

ioana.sandu@ki.se

I have been dreaming of becoming a scientist ever since I was a child. My interest in life sciences and the desire to explore the world drove me to complete my undergrad education outside Romania. I have studied Biochemistry and Bioengineering at the National Institute for Applied Sciences (Lyon, France, 2009 – 2014), where I fell in love with immunology and decided to complete my research master in therapeutic bioengineering in Bernard Verrier’s group, during which I studied the immune response induced by a nanoparticle-based vaccine. This experience motivated me to pursue my studies in immunology with the aim of getting a better understanding of fundamental CD8 T cell biology. I have then moved to Zurich, Switzerland for my graduate studies (2015 – 2019), followed by a postdoc (2020 – 2022) in systems immunology at ETH Zurich in Annette Oxenius’ and Manfred Claassen’s groups. My work focused on CD8 T cell heterogeneity and T cell receptor signaling during chronic viral infection. By using an experimental mouse model and computational tools, I could show that the differentiation of CD8 T cells is shaped by the tissue microenvironment, leading to different functional phenotypes. I was fascinated by their heterogeneity and decided to continue working on CD8 T cells to gain a better understanding of how this diversity is generated. In 2022 I joined Carmen’s group to learn how to barcode naïve CD8 T cells, which will enable me to investigate the heterogeneity of CD8 T cells at the clonal level.

Jyoti Pokharel, PhD student.

jyoti.pokharel@ki.se

As a kid, I wanted to become a doctor and “treat” diseases. After finishing school, I found it even more compelling to be involved in basic research and contribute to drug discovery and disease control. I moved to Bangladesh, where I got a B.Sc. degree in Biological Sciences and minor in Public Health at Asian University for Women (2015).  During my undergraduate years, I had few lectures on immunology and I couldn’t be more fascinated when I learned how our immune system fights pathogens and protects us. Without knowing what and where next, I took a year-long break and worked as a teaching assistant in my university (2015-2016).  During that time, I made up my mind that I wanted to study cancer biology and ended up in Germany where I studied Molecular Biosciences, major Cancer Biology, a combined degree from Universität Heidelberg and German Cancer Research Center (DKFZ). During my master’s program, I completed internships in different cancer types and fibrosis in different settings (epigenetics, genomics, and immunology). In 2018, I joined Jonathan Coquet’s lab at Karolinska Insitutet, Sweden which was my first time exposure to immunological studies. I knew right away, my heart was in immunology. I returned to Heidelberg and received my M.Sc. degree (2019). After finishing masters, I was looking for opportunities to work in immunology and more specifically, CD8T cells. Luckily, I was recommended to check Carmen’s work. And now, every day at work I love what I do or let’s say, I get to do what I love!

Iman Shryki, PhD student.

iman.shryki@ki.se

My journey in immunology started with my favourite childhood cartoon “once upon a time… life”. Since then, immune cells got my ultimate respect. They were the superheroes who saved the day! I studied pharmaceutical/biomedical sciences afterwards (Tishreen University, Syria 2005-2010). I thought that if biomedical scientists and our immune arsenal would join forces, humans would have a chance to win the battle against many diseases, including malignancies. During my first postgraduate studies (drug design & development master programme, Tishreen University, Syria. 2011-2015), I went back to immunological research and designed an anti-HIV protease inhibitor for my individual project. In 2015, I moved to Sweden to delve into cutting-edge biomedical research (Biomedicine master programme, Uppsala University, 2015-2017). In 2017, I joined Lena Ström’s group at Karolinska Institute where I developed a genuine interest in cellular biology. Today, I know that immunological research still is my main area of interest, and I am planning to pursue a career in immunology. Therefore, I joined Carmen Gerlach’s group in October 2018. In this inspiring environment, I am currently chasing every opportunity to learn more and, happily, advance further in my exciting journey.

Our lab is actively involved in research education at Karolinska Institutet in the field of immunology. This includes organization of the PhD course ‘Basic Immunology’, teaching on various aspects of T cell immunology and immunological techniques within PhD courses, the Biomedicine Master and Medicine program, as well as research supervision of PhD students.

We are grateful for the contribution from our funders:

Current

Knut and Alice Wallenberg Foundation

Cancerfonden

Vetenskapsrådet – Swedish Research Council (VR)

Ragnar Söderbergs stiftelse

Karolinska Institutet (MedS)

 

Past

Jeanssons Stiftelser

No-shows in T-cell responses are frequent for clones of low T-cell receptor affinity. van Gisbergen KPJM, Gerlach C. Eur J Immunol 2023 Mar;53(3):e2250305

T cell fate mapping and lineage tracing technologies probing clonal aspects underlying the generation of CD8 T cell subsets. Al Khabouri S, Gerlach C. Scand J Immunol 2020 Dec;92(6):e12983

Heavy Water Shedding Light on Antigen-Specific T Cell Responses. Eidsmo L, Gerlach C. Trends Immunol 2018 03;39(3):170-172

Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Natural Killer Cells in Vaccination. Neely HR, Mazo IB, Gerlach C, von Andrian UH. Cold Spring Harb Perspect Biol 2018 10;10(10):

The Chemokine Receptor CX3CR1 Defines Three Antigen-Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance and Homeostasis. Gerlach C, Moseman EA, Loughhead SM, Alvarez D, Zwijnenburg AJ, Waanders L, Garg R, de la Torre JC, von Andrian UH. Immunity 2016 12;45(6):1270-1284

Single cell behavior in T cell differentiation. Rohr JC, Gerlach C, Kok L, Schumacher TN. Trends Immunol 2014 Apr;35(4):170-7

Heterogeneous differentiation patterns of individual CD8+ T cells. Gerlach C, Rohr JC, Perié L, van Rooij N, van Heijst JW, Velds A, Urbanus J, Naik SH, Jacobs H, Beltman JB, de Boer RJ, Schumacher TN. Science 2013 May;340(6132):635-9

Nab2 regulates secondary CD8+ T-cell responses through control of TRAIL expression. Wolkers MC, Gerlach C, Arens R, Janssen EM, Fitzgerald P, Schumacher TN, Medema JP, Green DR, Schoenberger SP. Blood 2012 Jan;119(3):798-804

One naive T cell, multiple fates in CD8+ T cell differentiation. Gerlach C, van Heijst JW, Swart E, Sie D, Armstrong N, Kerkhoven RM, Zehn D, Bevan MJ, Schepers K, Schumacher TN. J Exp Med 2010 Jun;207(6):1235-46

Recruitment of antigen-specific CD8+ T cells in response to infection is markedly efficient. van Heijst JW, Gerlach C, Swart E, Sie D, Nunes-Alves C, Kerkhoven RM, Arens R, Correia-Neves M, Schepers K, Schumacher TN. Science 2009 Sep;325(5945):1265-9

Dissecting T cell lineage relationships by cellular barcoding. Schepers K, Swart E, van Heijst JW, Gerlach C, Castrucci M, Sie D, Heimerikx M, Velds A, Kerkhoven RM, Arens R, Schumacher TN. J Exp Med 2008 Sep;205(10):2309-18