Research Areas

Long Non-Coding RNAs in Development and Signal Transduction

Figure 1. Identification of lineage- or differentiation-stage–specific lncRNA gene–protein-coding gene co-expression modules. From Long non-coding RNA profiling of human lymphoid progenitor cells reveals transcriptional divergence of B cell and T cell lineagesCasero D, Sandoval S, Seet CS, Scholes J, Zhu Y, Ha VL, Luong A, Parekh C, Crooks GM. Nat Immunol. 2015;16:1282–1291.

Classification of Gene Expression Signatures in the Context of Aging and Chronic Inflammation

A better understanding of how changes in the cellular microenvironment of certain tissues (e.g., thymus, gut) affect molecular and differentiation pathways in immune cells constitutes a predominant theme of our research program. Further research in this field will be instrumental to identify novel biomarkers in, among others, childhood hematologic malignancies or immune dysfunctions in late adulthood (chronic inflammation). For instance, aging significantly alters the pattern of blood cell production in the bone marrow and, in particular, is known to result in reduced lymphopoiesis and increased myelopoiesis. Although, how changes in the bone marrow microenvironment influence these events are not fully understood.

Figure 2. Gene expression changes during the transition from PSC to hEMP to CD8SP T cells. From Organoid-induced differentiation of conventional T cells from human pluripotent stem cells. Montel-Hagen A, Seet CS, Li S, Chick B, Zhu Y, Chang P, Tsai S, Sun V, Lopez S, Chen HC, He C, Chin CJ, Casero D, Crooks GM. Cell Stem Cell. 2019 Mar 7;24(3):376-389.e8.

Host-Microbiome Interactions

Figure 2. Metabolic network modeling and taxa-metabolite associations. From Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolomeCasero D, Gill K, Sridharan V, Koturbash I, Nelson G, Hauer-Jensen M, Boerma M, Braun J, Cheema AK. Microbiome. 2017 Aug 18;5(1):105.

In many relevant cases, signals from our microbiome constitute an additional layer of regulation in the establishment and maintenance of normal tissue homeostasis. This additional layer requires a conceptual shift from the activities described above: now the normal microenvironment (self) also interacts with its symbiotic gut microbiota (quasi-self) and possibly pathogens (non-self). A proper understanding of these interactions is instrumental to gain insights into the etiology of some complex diseases, with IBD being a paradigmatic example.

Contact the Casero Lab

8730 Alden Drive
Thalians, E215
Los Angeles, CA 90048

David Casero, PhD