Casanova Lab
@casanovalab
We're a research lab at UT Southwestern Medical Center (TX) and Necker Hospital (Paris) studying human genetic and immunological determinants of infectious diseases.
7/ We will now study the role of antibodies in cancer and cancer avoidance by studying large international cohorts of individuals at high risk who avoided cancer and others at low risk who developed cancer.
2/ Paul Bastard at the @institutimagine.bsky.social leads the ATLAS team funded by Grand Cancer Challenges/Cancer Research UK, with support of the Breast Cancer Research Foundation, the Susan Wojcicki Foundation, and the Torrey Coast Foundation on Cancer Avoidance (cancergrandchallenges.org/atlas).
6/ Cycling has been an outlet since her time in NY and now it’s a platform for advocacy: Alexandra Kreins recently rode 800km from London to Glasgow with other paediatric professionals to campaign for cleaner air. She’s also passing her love for the outdoors on to her children.
5/ Now as group leader at GOSICH, Alexandra Kreins advances understanding of human T-cell immunity by defining how genetic variation disrupts thymic development and T-lymphopoiesis in children with IEI. doi.org/10.1016/j.mo... doi.org/10.1016/j.cl...
/ Alexandra Kreins finished medical training in Zurich, became a Paediatrician, then continued training at Great Ormond Street Hospital, in London. In 2020, she returned to @casanovalab.bsky.social for the first time thanks to a @wellcometrust.bsky.social Clinical Research Career Development Award.
3/ Her time in the lab inspired a pivot from Internal Medicine to Paediatrics and finally to Paediatric Immunology. Beyond training in IEI, Alexandra Kreins gained community: “Every postdoc from my 'mycobacterial cohort' is now an independent PI doing amazing and inspiring research.”
2/ Alexandra Kreins was a grad student in our NY lab from 2009-13. She co-authored several publications on the pathophysiology of novel IEI in the JAK-STAT signalling pathways. Her thesis was on the characterization of human TYK2 def. Her bench speaks for itself. doi.org/10.1084/jem....
1/ Spotlighting our former trainee Alexandra Kreins - a clinician-scientist specializing in IEI and cellular therapies @ UCL Great Ormond Street Institute of Child Health (GOSICH). She is also an Honorary Consultant in Paediatric Immunology at Great Ormond Street Hospital (GOSH), London
8/ We also found that they were common in the general population with a prevalence of about 0.4% and 4% under and above the age of 70 years.
7/ These findings have been replicated in at least 30 independent cohorts worldwide.
3/ As a clinician scientist, Janine Reichenbach shared our passion for rigorous translational science. She said her training shaped her future career and opened doors. Her connections with past and present lab members permits ongoing collaboration & "true scientific friendship."
1/ Our next lab alumna is Janine Reichenbach. Her impressive list of titles includes Dep. Dir. at the Institute for Regenerative Medicine (IREM) of University of Zurich & Head of both the Div. of Gene and Cell Therapy (IREM) & the Div. of Somatic Gene Therapy at University Children's Hosp. Zurich.
6/ Outside of science, @bogunoviclab.bsky.social loves dancing tango! He denied having a tango photo (I asked 😉) but did share a lovely one of his team below. Keep bringing your great passion to the dancefloor and to the lab, Dusan!
2/ @bogunoviclab.bsky.social worked hard in our mycobacterial group w/ Stephanie Boisson-Dupuis. His memories include a trip to the lab on his way to be best man at his friend’s wedding (below) and performing so many PCR & SANGER assays that he got carpel tunnel and had to ice his hands each night!
1/ Spotlight on our former trainee Dusan Bogunovic (@bogunoviclab.bsky.social), a postdoctoral fellow in our NY lab from 2010-13 and now Professor of Pediatrics, Vice Chair for Basic Research, and Director of the Center for Genetic Errors of Immunity at @columbiauniversity.bsky.social.
6/ Other than science, Yi-Hao Chan has a strong passion for running. He joined the JPMorgan Chase Corporate Challenge every year that he was in New York, roping in lab friends to participate. He also loves a good meal and has fond memories of shared meals with the @casanovalab.bsky.social!
5/ After training, Yi-Hao Chan joined @astar-idlabs.bsky.social in Singapore as a PI, receiving the prestigious NRF Fellowship to continue his work on host determinants of life-threatening viral diseases with his new team. He also won the Young Scientist Award at the PSTA 2025 to top it all off.
4/ Yi-Hao Chan reflected that he worked hard in the lab but that it was an enriching period in his career. “We had strong camaraderie and openly discussed scientific problems, hypotheses and ludicrous ideas. It helped that there were many pizzerias near RU where we could wind down!”
2/ A Post-Doc Fellow (2021-24) in our NY lab, Yi-Hao Chan trained with @ShenYingZhang1.bsky.social & me, uncovering human TMEFF1 as the 1st discovered restriction factor for HSV-1 in the brain, and DBR1 deficiency as the 1st genetic etiology for isolated SARS-CoV-2 brainstem viral encephalitis.
1/ We are continuing to highlight the accomplishments of our amazing former trainees. Next is Yi-Hao Chan, now PI at @astar-idlabs.bsky.social, working on the host determinants underlying life-threatening viral diseases (esp. arthropod-borne). www.a-star.edu.sg/idlabs/peopl...
19/ More recent findings, building on the 2004 and 2020 papers (steps 2 and 5 in table above), suggest a revised architecture of human infections, with “monogenic infections” in young patients and “autoimmune infections” in older patients.
15/ There are now auto-antibodies neutralizing 6 different cytokines: each of them underlies a specific set of infections, like those seen in patients with inborn errors of the corresponding cytokine.
12/ Proportions of cases due to monogenic lesions or their autoimmune phenocopies vary per infection within each of the five categories. The best understood common infectious disease is now West Nile virus encephalitis, due to auto-Abs against type I IFNs in 40% of patients.
10/ While primary immunodeficiencies were long known to underlie multiple infections in individual patients, specific infections striking otherwise healthy patients were only reported from 1996 onward to be due to monogenic lesions.
9/ In this table we outline the monogenic architecture of human infections developed from 1996 onward. From this genetic angle, there are five categories or steps of infection.
7/ Surprisingly, monogenic inborn errors of the complement were reported earlier in patients with invasive Neisseria infections, from the 1970s onward, but these findings did not launch the search for “monogenic infections”.
4/ The infection enigma applies to all plants and animals. It was tackled by classical geneticists (not microbiologists or immunologists), and later by molecular geneticists, who discovered disease-causing monogenic lesions in mice (1985), in plants (1993), and in humans (1996).
2/ The key problem in the field of human infections was posed around 1900, it’s the “infection enigma”. Only a small proportion of people infected by any microbe develop life-threatening disease.
10/ Texas is centrally located within the southern US. Dallas is a transportation hub with all major US cities < a 4-hr flight away. Dallas Fort Worth Intl. Airport connects the region to 39 major hubs, including all capital cities in Asia, Oceania, Latin America, and Europe.
9/ Dallas, the birthplace of the frozen margarita machine, is the 9th largest US city (4th when combined with Fort Worth), has the largest contiguous urban arts district in the US, and boasts more restaurants per capita than NYC (more studies are needed to confirm this claim! 😉).