Active Research Projects
Defining the role of cell migration in human NK cell differentiation
What are the contact-dependent molecular mechanisms that regulate the step-wise maturation of human NK cells? To address this question we use high-resolution confocal and super-resolution microscopy to dissect the interactions between developing human NK cells and stromal and accessory cells. Extended live cell imaging provides information into the kinetics of NK cell motility and proliferation. A better understanding of the regulated acquisition of human NK cell function will aid in the design of strategies to improve immunotherapy as well as understand how this process goes wrong in human disease.
Understanding requirements for human NK cell maturation through the study of primary immunodeficiency
Human NK cells are key to the innate immune response to viral infection and malignancy. Their importance is demonstrated by severe disease found in rare individuals with inborn errors of immunity that lead to impaired NK cell maturation or function. Through collaboration with Dr. Jordan Orange, we perform basic research on the functional mechanism of NK cell deficiency in patients with primary immunodeficiency of both known and unknown etiologies. Through this work we aim to better understand the biological underpinnings of human disease and identify novel requirements for NK cell development. This has led to basic research on the role that the eukaryotic DNA helicase and cell proliferation play in human NK cell maturation.
The role of CD56 in human NK cell function
Despite its use as the predominant phenotypic marker of human NK cells, the functional role of CD56, a member of the Ig superfamily, has not been well described. Through our work on the developmental synapse we have identified CD56 as playing an important role in human NK cell function. Current work in our lab is ongoing to elucidate this role through the use of CRISPR-Cas9 gene editing.
Expertise and techniques
Our research is focused on the study of human innate immune cells, and we strive to implement cutting-edge technologies to better model, understand and dissect human immune cell function. We are experienced in the use in vitro differentiation to generate human NK cells from CD34+ precursors and are extending our reach through use of gene editing and induced pluripotent stem cell (iPSC) systems. In addition, we use multi-scale, multi-dimensional imaging and image analyses to probe immune cell biological function. This includes the use of super-resolution and TIRF microscopy, as well as confocal and long-term live cell imaging by widefield microscopy. We are conscientious, rigorous and collegial members of our scientific and clinical communities; as such we will always share openly our data and resources to the fullest extent possible.