Liza Konnikova, MD PhD
Our group focused on the development and regulation of early life immunity and its role in human health and disease. We are trying to answer basic questions about human immune development that include:
Our NIH and private foundations funded group focuses on understanding host and environmental drivers of development and regulation of circulating and mucosal immunity and their roles in human health and disease. My interests began during my postdoctoral training when, I developed a methodology for cryopreserving viable intestinal tissue (Mucosal Immunology, 2018). Our work demonstrated that intestinal organoids can be generated from cryopreserved tissue at rates similar to those of fresh tissue and showed excellent inclusion of intestinal immune populations. To optimize our ability to study infant populations, we designed a protocol to perform multi-omic assays from two drops of blood or ~100 μL. This has allowed us to optimize biological data collection from a highly vulnerable patient population, premature infants, to study their immune development at an unprecedented granularity.
Using a systems biology approaches and cutting-edge techniques, such as imaging and suspension mass cytometry and single cell RNA sequencing, my group is deciphering how mucosal immunity develops at barrier sites such as the placenta and the GI tract and what causes it to become disordered and cause disease. To this end, we have established a large biorepository (over 10,000 samples) of control and diseased cryopreserved tissue across the human lifespan from 12 weeks gestational age to elderly adults. Using tissue from our biobank, we studied the development of human fetal intestinal and placental immunity (Stras et al., Developmental Cell, 2019; Egozi et al., Nature Medicine, 2021; Toothaker et al., Development, 2022) demonstrating presence of functional memory T cells as early as the second trimester. To pursue the source of antigens priming of these T cells, we are collaborating with Profs. Koren and Khatib’s groups (Bar Ilan University, Israel) and are studying the fetal intestine associated microbiome and metabolome. Those investigations provided the first evidence that human fetal tissue contains abundant and diverse bacterial metabolites in the absence of a detectable microbiome (Li and Toothaker et al, JCI Insight, 2020; Kennedy et al., Nature 2023; Kennedy et al., Cell, 2021). To expand these studies, we plan to study how the intestinal microbiome effects neonatal health. Furthermore, I have joint forces with Prof. Isabelle Sirois group (University of Montreal, Canada) to define the in utero immunopeptidome. This work has yielded some exciting preliminary results suggesting microbial peptides are also found in utero.
In summary, the goal of our scientific studies is to define early life human immune development and to understand its dysregulation in disease. To that end, our group has made key contributions that have shifted the paradigm of how we think about early life immunity from an immature naïve state to a functional and specifically adapted to the challenges of early life one (Stras et al., Dev Cell, 2019, Egozi et al., Nature Medicine, 2021; Toothaker et al., Development, 2022; Egozi et al., Plos Bio, 2023, Wu et al., Mucosal Immun, 2024) and identified global mucosal and systemic cellular dysregulation and unique immune and epithelial populations in necrotizing enterocolitis and inflammatory bowel disease (Mitsialis, Gastroenterology, 2020; Olaloye et al., JEM, 2021; Egozi, Plos Bio, 2023).
- What are the functions of immune cells in early life?
- How early does human immune system starts to develop?
- Is the early life immune system compartmentalized? i.e. Does it differ between organs and various mucosal sites?
- What are the antigens priming early like T-cells?
- What is the cross talk between the various cellular components that maintains homeostasis?
- What is the role of environmental stimuli (microbiome, nutrition, etc) in shaping the early life immune system?
- How do fetal and postnatal immune cells contribute to disease susceptibility
Our NIH and private foundations funded group focuses on understanding host and environmental drivers of development and regulation of circulating and mucosal immunity and their roles in human health and disease. My interests began during my postdoctoral training when, I developed a methodology for cryopreserving viable intestinal tissue (Mucosal Immunology, 2018). Our work demonstrated that intestinal organoids can be generated from cryopreserved tissue at rates similar to those of fresh tissue and showed excellent inclusion of intestinal immune populations. To optimize our ability to study infant populations, we designed a protocol to perform multi-omic assays from two drops of blood or ~100 μL. This has allowed us to optimize biological data collection from a highly vulnerable patient population, premature infants, to study their immune development at an unprecedented granularity.
Using a systems biology approaches and cutting-edge techniques, such as imaging and suspension mass cytometry and single cell RNA sequencing, my group is deciphering how mucosal immunity develops at barrier sites such as the placenta and the GI tract and what causes it to become disordered and cause disease. To this end, we have established a large biorepository (over 10,000 samples) of control and diseased cryopreserved tissue across the human lifespan from 12 weeks gestational age to elderly adults. Using tissue from our biobank, we studied the development of human fetal intestinal and placental immunity (Stras et al., Developmental Cell, 2019; Egozi et al., Nature Medicine, 2021; Toothaker et al., Development, 2022) demonstrating presence of functional memory T cells as early as the second trimester. To pursue the source of antigens priming of these T cells, we are collaborating with Profs. Koren and Khatib’s groups (Bar Ilan University, Israel) and are studying the fetal intestine associated microbiome and metabolome. Those investigations provided the first evidence that human fetal tissue contains abundant and diverse bacterial metabolites in the absence of a detectable microbiome (Li and Toothaker et al, JCI Insight, 2020; Kennedy et al., Nature 2023; Kennedy et al., Cell, 2021). To expand these studies, we plan to study how the intestinal microbiome effects neonatal health. Furthermore, I have joint forces with Prof. Isabelle Sirois group (University of Montreal, Canada) to define the in utero immunopeptidome. This work has yielded some exciting preliminary results suggesting microbial peptides are also found in utero.
In summary, the goal of our scientific studies is to define early life human immune development and to understand its dysregulation in disease. To that end, our group has made key contributions that have shifted the paradigm of how we think about early life immunity from an immature naïve state to a functional and specifically adapted to the challenges of early life one (Stras et al., Dev Cell, 2019, Egozi et al., Nature Medicine, 2021; Toothaker et al., Development, 2022; Egozi et al., Plos Bio, 2023, Wu et al., Mucosal Immun, 2024) and identified global mucosal and systemic cellular dysregulation and unique immune and epithelial populations in necrotizing enterocolitis and inflammatory bowel disease (Mitsialis, Gastroenterology, 2020; Olaloye et al., JEM, 2021; Egozi, Plos Bio, 2023).