Neurobiology of Stress and Treatment Response – Juan Pablo Lopez group

Through a series of innovative concepts, tools and techniques, our laboratory seeks to understand and characterize the molecular mechanisms, cellular circuits, and behavioral correlates, associated with stress-related psychiatric disorders and their treatments.

Group picture of lab members outside in front of the Aula, KI Campus Solna.

Research and activities

Schematic overview
Figure 1: Schematic overview of research programme in the Lopez Laboratory. From genes to behaviour: A translational psychiatry approach. Photo: Juan Pablo Lopez.

Using wild-type and genetically modified animal models, our research programme tackles psychiatrically-relevant questions such as:

  • Why does one individual develop psychiatric symptoms, whereas another does not?
  • What are the relevant critical or sensitive periods of development where adversity becomes neurobiologically embedded?
  • What are the neurobiological mechanisms underlying clinical improvement?
  • What are the biological correlates of treatment response?

Our strategy consists of implementing a combination of novel, automated, and high-throughput behavioral and molecular experimental approaches to:

  1. Elucidate the mechanisms by which stressors are perceived and processed into molecular, neuroendocrine and behavioral responses, under healthy and pathological conditions, in males and females.
  2. Characterize critical time windows and neurobiological circuits contributing to the molecular, cellular and behavioral outcomes associated with susceptibility and resilience to stressful stimuli, as well as treatment response.
  3. Identify and characterize “activated” cell populations and circuits involved in the regulation of stress responses and rapid-acting antidepressant effects.
  4. Identify novel behavioral and molecular predictors of stress susceptibility and treatment response.

To achieve these objectives our laboratory implements a wide range of techniques, such as (a) state-of-the-art transcriptomics, including “bulk” and single-cell resolution, (b) behavioral mouse models of stress and anxiety, (c) automated behavioral tracking and analysis systems of complex behaviors for groups of mice, (d) diverse transgenic mouse models, and (e) viral-mediated gene manipulations in behaving mice.

Schematic overview of research methods
Figure 2: Schematic overview of research methods used in the Lopez Laboratory. Increasing the resolution in stress neurobiology: From single cells to complex behaviours. Photo: Juan Pablo Lopez.
Animated film showing behaviour and moving patterns of mice.
Screenshot of example video: Tracking - ROIs visits.

Projects

For information about ongoing research projects, please email Juan Pablo Lopez at jpablo.lopez@ki.se.

Research support

Current funding

  • European Research Council (ERC), Starting Grant – LS5
  • The Swedish Research Council (VR), Starting Grant – MH-12
  • The Swedish Brain Foundation (Hjärnfonden) – Research Grant
  • The Swedish Society for Medical Research (SSMF) – Starting Grant
  • KIRI Fellow, Postdoctoral project – Research Grant
  • The Strategic Research Area Neuroscience (StratNeuro) – Starting Funds
  • Karolinska Institutet – Starting Grant

Past funding

  • EMBO Long-Term Postdoctoral Fellowship, European Commission
  • Alexander von Humboldt Foundation Postdoctoral Fellowship, Germany 
  • CAN-BIND Postdoctoral Fellowship, Canada
  • CIHR Doctoral Award, Canada 
  • FRQS Doctoral Award, Quebec
  • Lloyd Carr-Harris Doctoral Fellowship, Canada

Publications

Selected publications

MicroRNAs 146a/b-5 and 425-3p and 24-3p are markers of antidepressant response and regulate MAPK/Wnt-system genes.
Lopez JP, Fiori LM, Cruceanu C, Lin R, Labonte B, Cates HM, Heller EA, Vialou V, Ku SM, Gerald C, Han MH, Foster J, Frey BN, Soares CN, Müller DJ, Farzan F, Leri F, MacQueen GM, Feilotter H, Tyryshkin K, Evans KR, Giacobbe P, Blier P, Lam RW, Milev R, Parikh SV, Rotzinger S, Strother SC, Lewis CM, Aitchison KJ, Wittenberg GM, Mechawar N, Nestler EJ, Uher R, Kennedy SH, Turecki G
Nat Commun 2017 05;8():15497

DCC Confers Susceptibility to Depression-like Behaviors in Humans and Mice and Is Regulated by miR-218.
Torres-Berrío A#, Lopez JP#, Bagot RC, Nouel D, Dal Bo G, Cuesta S, Zhu L, Manitt C, Eng C, Cooper HM, Storch KF, Turecki G, Nestler EJ, Flores C
Biol Psychiatry 2017 02;81(4):306-315

Biomarker discovery: quantification of microRNAs and other small non-coding RNAs using next generation sequencing.
Lopez JP, Diallo A, Cruceanu C, Fiori LM, Laboissiere S, Guillet I, Fontaine J, Ragoussis J, Benes V, Turecki G, Ernst C
BMC Med Genomics 2015 Jul;8():35

miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment.
Lopez JP, Lim R, Cruceanu C, Crapper L, Fasano C, Labonte B, Maussion G, Yang JP, Yerko V, Vigneault E, El Mestikawy S, Mechawar N, Pavlidis P, Turecki G
Nat Med 2014 Jul;20(7):764-8

Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex of depressed suicide completers.
Lopez JP, Fiori LM, Gross JA, Labonte B, Yerko V, Mechawar N, Turecki G
Int J Neuropsychopharmacol 2014 Jan;17(1):23-32

Epigenetic regulation of BDNF expression according to antidepressant response.
Lopez JP, Mamdani F, Labonte B, Beaulieu MM, Yang JP, Berlim MT, Ernst C, Turecki G
Mol Psychiatry 2013 Apr;18(4):398-9

Staff and contact

Group leader

All members of the group

Contact and visit us

Mailing address: Karolinska Institutet, Department of Neuroscience, 171 77 Stockholm

Visiting address (visitors, couriers, etc.): Karolinska Institutet, Biomedicum, Quarter D7, Solnavägen 9, 171 65 Solna

Delivery address (goods, parcels, etc.): Biomedicum, Tomtebodavägen 16, 171 65 Solna

Biomedicum, Karolinska Institutet, Solnavägen 9

Meet our team

Dr. Juan Pablo Lopez

Assistant Professor

About me: I am an Assistant Professor in the Department of Neuroscience. I received my undergraduate degrees in Psychology and Biology from Florida International University (Miami, USA), my PhD from McGill University (Montreal, Canada), and a postdoc at the Max Planck Institute of Psychiatry (Munich, Germany). I am interested in understanding and characterizing the molecular mechanisms, cellular circuits, and complex behaviors, associated with stress-related psychiatric disorders and their treatments, using animal models. When I am not working in the lab, I love spending time with family, smoking meats (BBQ) for friends, hiking in the mountains, and training Brazilian Jiu-Jitsu.

Dr. Paula Fontanet

Research Specialist

About me: Hi, I’m Paula. I was born in Buenos Aires, Argentina. I received my PhD from Buenos Aires University under Fernanda Ledda's supervision. In 2017, I moved to Sweden to pursue a Postdoc at Karolinska Institutet with Prof. Francois Lallemend. In 2024, I joined the Lopez Lab as a Research Specialist. I am motivated by its innovative research approach for a better understanding of stress-related psychiatric disorders and their treatments. Outside the lab, I enjoy spending time with my family and friends, doing as many outdoor activities as possible, when the weather here in Sweden allows it. I am always up for a chat about science and or a friendly conversation.

Dr. Fatemeh Sadat Zolfaghari

Research Assistant

About me: I'm Fatemeh, a hold a PhD in Exercise Physiology. Currently, I am a research assistant in the Lopez Laboratory. I am interested in exploring neurochemical and molecular markers in animal models of stress and anxiety. When I'm not immersed in scientific pursuits, I find joy in photography. Writing literary texts and poetry has been a cherished activity of mine since I was 9 years old. Additionally, I am deeply passionate about engaging in various sports activities.

Serena Gasperoni

PhD student

About me: My name is Serena, I am currently a PhD student at KI, and hold a Master's degree in Pharmaceutical Biotechnology from the University of Bologna. My PhD project focuses on understanding the behavioral language, molecular mechanisms, and cellular circuits responsible for the fast-acting and sustained antidepressant effects of psychedelic compounds, using mouse models of chronic stress. When I'm not in the lab, I like spending time in nature, playing the guitar and doing yoga.

Xiuqi Ji

Research Assistant

About me: I am Xiuqi, and I hold a joint MSc in Molecular Techniques in Life Science from KTH, Karolinska Institute, and Stockholm University. I am currently a research assistant in the Lopez Lab. I am interested in understanding how exposure to stress during adolescence can affect susceptibility or resilience to stress later in life. I have a strong interest in applying and developing bioinformatics methods to biomedical and disease research. Outside of the lab, I enjoy reading, spending time in nature, and am enthusiastic about film and music.

Nicole Sabouné

Research Assistant

About me: My name is Nicole and I have always had a great love for science with a dream to pursue a career in research. From Stockholm University, I hold a MSc in neurochemistry with molecular neurobiology, with a focus on neuroendocrinology. In the Lopez lab, I am interested in investigating how early life adversity can shape our brains and behavior later in life. When I’m not present in the lab, I’m most certainly in the studio writing music, reading books or hanging out with my friends.

Maité Creteur

Research Intern/MSc Student

About me: I am a Master student in the ‘Translational Physiology and Pharmacology’ program at KI. In the Lopez lab, I am contributing to a machine-learning project aimed at automatically tracking the behaviour of groups of laboratory animals (mice and pigs) treated with novel and rapid-acting antidepressants, in a semi-naturalistic environment. In my spare time, you can find me in nature, where I am enjoying a good book or hiking.

Cheng Yang

Research Intern/MSc Student

About me: I am Cheng. I am a student in the Master’s Programme of Translational Physiology and Pharmacology at Karolinska Institutet, Sweden. In the Lopez lab, I assist in the validation of machine-learning prediction models and the annotation of videos of mice displaying behaviors of interest. During my spare time, I enjoy doing sports such as basketball and table tennis. Meanwhile, I like spending time playing video games and watching anime.

Choham Sudre-Chinsky

Research Intern/MSc Student

About me: My name is Choham and I am a second-year master’s student at the ENS de Lyon. My internship at the Lopez Lab involves expanding the use of the complex analytical tools of the lab to larger cohorts of freely moving mice. These tools are designed to study the behavior of mouse models of stress. In my free time, I enjoy reading, playing the saxophone, and exchanging ideas with my friends. I also like to discover new places and learn new languages.

Manar Manla Hasan

Research Intern/Medical Student

About me: I am undertaking an introductory research course here at KI alongside my studies in the medical program. In the Lopez lab, I assist in optimizing behavior detection in freely moving groups of mice within an enriched environment by annotating videos containing multiple behaviors of interest. During my free time, I enjoy participating in outdoor activities and further exploring Stockholm.

Otto Boldemann

Research Intern/Medical Student

About me: I'm a second-year medical student at KI with a growing enthusiasm for research. Currently, I am contributing to an engaging project focused on machine learning-assisted behavioral phenotyping in mice. In this capacity I identify behaviors, in hopes of providing insights to the research team's efforts. When I'm not immersed in my academic pursuits, I find joy in the company of friends and my girlfriend. Additionally, I have a passion for sports such as football and table tennis, as well as strategic games like chess and board games.

Thea Schillen

Research Intern/Highschool Student

About me: I'm a second-year medical student at KI with a growing enthusiasm for research. Currently, I am contributing to an engaging project focused on machine learning-assisted behavioral phenotyping in mice. In this capacity I identify behaviors, in hopes of providing insights to the research team's efforts. When I'm not immersed in my academic pursuits, I find joy in the company of friends and my girlfriend. Additionally, I have a passion for sports such as football and table tennis, as well as strategic games like chess and board games. 

Former lab members

2023

  • Josefin Kenrick, Research Assistant
  • Julio Eduardo Cáseres Pajuelo, MSc Student (Erasmus+), Universidad Autónoma de Madrid, Spain
  • Lucas Sébastien Dumargne, MSc Student, ENS Lyon, France

2022

  • Alix Bonard, MSc Student (Erasmus+), Sorbonne University, Paris, France

Work with us

We are looking for talented graduate students and postdocs interested in exploring the neurobiology of stress and antidepressant treatment response.

We are particularly interested in candidates with experience in one, or more, of the following fields: molecular biology, functional genomics, pharmacology, clinical/translational neuroscience, behavioral neuroscience, bioinformatics, or computer science.

If you are interested in joining our lab, please send an email to Juan Pablo Lopez at jpablo.lopez@ki.se.

Please enclose the following

  • Academic CV
  • Brief cover letter (or statement) describing your motivation, career goals, and what you hope to achieve in our lab
  • Name and full contact information for 2-3 references

Applications at all levels are welcome!

In the media

Published news items in media outside of KI.

2024

In search for more efficient treatments for psychiatric disorders with ERC starting grant, Stockholm Science City (SSCI), 1 Februrary 2024

2023

Traces of Trauma in the Young Brain – and How to Erase Them, Weizmann Institute of Science, Weizmann Wonder Wander Science news and Culture, 3 December 2023

Vive la Différence: Brain Cells of Males and Females Respond Differently to Chronic Stress, Weizmann Institute of Science, Weizmann Wonder Wander Science news and Culture, 1 August 2023