projects

Mapping the Statistics of the Human B cell system

Ivana Cvijovic and I created the first systems level perspective of the human B cell system. B cells create antibodies which provide adaptive protection to an individual against pathogens, and are the basis for how vaccines work. Two major types of B cells are responsible for the durability of antibody protection: memory B cells and long-lived antibody secreting cells. Long-lived antibody secreting cells are laregly uncharacterized in the context of the human immune system because they are not found in the peripheral blood, making that they are difficult to study. Thus, we created a unique multi-tissue dataset from human organ donors capable of quantitatively answering outstanding questions about the long-term B cell memory.

One of our major findings is long-term antibody memory doesn’t follow a temporal switch model, as had been suggested based on mouse data. Instead, it occurs uniformly throughout the immune response. This insight could only emerge from analyzing hard-to-sample tissues like the spleen, lymph nodes, and bone marrow, highlighting the importance of a multi-tissue approach.

Another significant discovery was that proliferative antibody-secreting cells appear uniquely licensed to circulate amongst all tissues we sampled. These cells, unlike other B cell types, travel across different tissues and may be key in inter-tissue immune communication, suggesting a new perspective on antibody feedback across the body. You can read the full paper here.

Leveraging lineage tracing to understand cell reprogramming

In this study, I investigated a fundamental question in developmental biology: how do cells integrate external signals with their intrinsic cellular state during the process of cell reprogramming? To address this, I used human B cells, a type of immune cell, as a model system.
Over the course of a 12-day reprogramming experiment, I employed single-cell genomics techniques to quantify the relative contribution of the cells’ intrinsic status to their response to reprogramming stimuli. The results revealed that intrinsic effects played a significant role in determining the outcome of the reprogramming process. Despite all cells being subjected to the same extrinsic stimulus, the reprogrammed cell populations exhibited a high degree of diversity in their final states. This apparent stochasticity, in the reprogramming outcomes was intriguing. However, upon closer examination, it became evident that groups of cells descended from the same initial cell often adopted similar fates, indicating that even subtle differences in the state of an initial cell are propagated through clonal expansion and ultimately can drive reprogramming outcomes. These findings have significant implications for the long-standing goals of cellular reprogramming and controlling cell fate for applications in cell-based therapies and tissue engineering. By gaining a deeper understanding of how cells integrate their intrinsic properties with external signals, we can develop more precise and efficient methods for directing cell fate and function. You can download the full paper and processed data.

Creating the datasets to enable Molecular Medicine

I’m a key contributor to the Tabula Sapiens Consortium, where we’ve created a multi-organ, single-cell transcriptomic atlas of humans. This atlas is a valuable resource for training foundation models of biology and understanding the molecular basis of diseases. My role has run the full-stack of the project from procuring organs, processing them into single-cell suspensions, preparing sequencing libraries, and analyzing the vast datasets created. I’ve been partiularly interested in analyzing the immune cells across tissues. By studying these cells the context of the broader human atlas, we’re gaining new insights into this complex system’s function and regulation. You can find the full paper here.

leveraging the my n-of-one neural network to advance the state of chillwave

I make ambient chillwave music under the name maiklo.