Welcome to the Kim Lab

Optical imaging of immunity

Host immune response against infection and inflammation:

A) The maintenance of homeostatic immune surveillance and the development of effective adaptive immune responses require that T cells cross tissue barriers and move throughout the body, migrating in and out of the bone marrow, lymphoid and non-lymphoid tissues, under both normal and infected or inflamed conditions. The efficient trafficking of activated effector T cells into peripheral non-lymphoid tissues is key to enact their protective functions. Insufficient T cell activity contributes to impaired local adaptive immunity, recurrent infections and delayed wound healing, whereas excessive T cell recruitment leads to an exaggerated inflammatory response and the associated tissue damage. Importantly, successful early local innate immune response is critical for elicitation of T cell effector functions at the peripheral tissue sites. Therefore, it is likely that the type of innate cells, mode of early innate responses, and associated local inflammatory mediators will all impact on the molecular mechanisms by which effector T cells successfully move into the inflamed tissues. Our objective is to determine how the early innate immune responses prime and remodel the tissue microenvironment prior to effector T cell homing and how the tissue-specific inflammatory cues further modify the chemokine signals, integrin activation and migration of T cells.

B) Severe sepsis, a systemic inflammatory response to infections associated with acute organ dysfunction, is an increasing cause of morbidity and mortality among children and adults. Neutrophil recruitment during sepsis is key for host defense against infection and injury, and precise regulation of the interaction between neutrophils and components of the vascular layer is essential to minimize excessive damage to vascular walls during a localized inflammatory response, thus to sustain vascular homeostasis and control microvessel permeability. During severe sepsis, however, this system fails and massive infiltration of active neutrophils followed by exaggerated inflammatory response participates in the pathogenesis of multi-organ system failure (MOSF) through vascular injury and host tissue damage. We will identify the molecular events that cause destruction of each vascular barrier during neutrophil recruitment and develop novel therapeutic approaches to restore homeostasis.

Optical control of immunity

Cancer immunotherapy: Immunotherapy for cancer is an exciting topic, as it involves stimulating a patient’s own immune system to fight the malignancy. We are using a process called “optogenetics” to try to improve the response rates for immunotherapy. Three underlying issues challenge immunotherapy: First, cancer cells are smart and evasive, often hiding from the immune system. Second, tumors suppress the immune system, presenting another challenge for the anti-cancer T cells once they’ve located a tumor. Third, immunotherapy often comes with side effects. We are studying light and optics as a tool to bypass all three obstacles. All cytolytic T cells (e.g. CD8 T cells) contain effector molecules that can directly kill cancer cell. To make sure the T cells know where to find their target, Our lab has engineered T cells that respond to light. By implanting a light source — an LED chip that our group also invented — into the body of a mouse, we demonstrated that light can guide the T cells to the cancer cells. Once there, the light source also boosts the toxic, biological reaction within the T cells, better positioning them to wipe out their target cancer. And finally, we will invent a molecular safety switch (also based on light) that causes T cells to self-destruct when their job is done, preventing severe side effects resulting from the immune system remaining in overdrive. The achievement of functional hybrid photosensitive receptors represents a real tour de force, and opens up many analytical and therapeutic possibilities.  This is particularly important because of the increasing success of cancer immunotherapies – Our optogenetics approaches will provide further capabilities to such approaches.