Chi Keung Lam

Biological Sciences

Chi Keung Lam

Assistant Professor

lamcg@udel.edu

302-831-3165

Office: 221 BPI
Lab: 245 BPI

Resources and Links

Chi Keung Lam's Google Scholar Publications

Lam Lab Website

Lab-Lab Cardio Centric

Education

B.S. - Purdue University
Ph.D - University of Cincinnati
Post-doctoral - Stanford University
Instructor - Stanford University

Research Interests

Heart disease is one of the top killers in the United States and worldwide. With more than 5 millions heart failure cases per year in US, it is alarming that half of those patients cannot survive beyond five years after diagnosis. One major issue is that current therapies are not developed to target the etiology of cardiomyopathy. The long-term goal of my lab is to identify disease mechanisms in various hereditary and acquired cardiac diseases, and develop targeted therapeutic to improve clinical outcome.

Unlike other organs, heart needs to continuously contract and relax rhythmically to ensure proper blood supply to the rest of the body. The center of this regulation is the rise and fall of calcium ions within the cell, as it is essential for the shortening and re-lengthening of myofilaments. Dysregulation of this rhythmic cycle will reduce the efficiency of the pumping action. Furthermore, calcium is also an essential mediator in cell survival/death signaling. Ectopic calcium response can have detrimental outcome in the heart, as it is difficult to reverse damage caused by unwanted cell death due to its limited regenerative capacity. My lab is interested in understanding how calcium is regulated in each compartment in the cardiac cells. By understanding the regulatory machinery in local milieu, we can further explore how calcium dysregulation trigger various stress response. Using both mouse models and human induced pluripotent stem cell (iPSC) platform, we examine the effect of modulating our target protein or gene in cardiac physiology and pathophysiology. The combination of human iPSC and animal studies can complementarily validate mechanisms with human and rodent genetics. The scalable iPSC platform and engineered heart tissue technology also allow us to test compounds or biologics effectively to facilitate drug discovery.

Current Projects

1. Identifying novel regulators for calcium kinetics.

Intracellular calcium regulation is essential to maintain normal contractile function of cardiac cells. Calcium dysregulation have been shown to be a hallmark in various types of cardiac diseases. While the importance of calcium in cardiac function has been appreciated for very long time, we still lack the understanding on how calcium is precisely regulated under various physiological conditions. This prevents us from developing proper strategy to correct the fundamental issue. Previously, my works have demonstrated apoptotic protein HAX-1 form a chaperone complex that regulates sarcoplasmic reticulum (SR) calcium handling. With proteomic and genomic approaches, my lab is interested in identifying new regulators for calcium control and examining their shift of function in different diseased conditions.

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2. Deciphering the crosstalk between calcium circuit and stress signaling pathways in diseased hearts.

Given the central role of calcium in regulating various cellular responses, it is important to understand how cardiac cells regulate local calcium signaling to activate signaling in the milieu without affecting other processes. Moreover, my works previously identified that SR calcium regulatory complex (PLN/SERCA/HAX-1) can crosstalk with endoplasmic reticulum (ER) stress response sensor, IRE-1. Disruption of this crosstalk is capable to sensitizing cardiac cell to cell death. Thus, one major research direction in my lab is to identify and understand novel crosstalk, which allows us to gauge the feasibility to simultaneously target two diseased mechanisms in failing hearts.

3. Understanding the mechanism of cardiotoxicity induced by current medication and identify therapeutic options.

Cardiotoxicity, such as reduced cardiac function and induction of arrhythmia, is a major cause for drug withdrawal in the market. Furthermore, the application of promising treatment can be limited by black box warning with adverse cardiovascular complication. Classic examples are anthracycline and tyrosine kinase inhibitors, which are commonly used in cancer therapy. My lab is interested in identifying the cardiac-specific mechanisms induced by those agents. It will allow us to develop strategy to prevent the adverse side effects in the heart but retain the cancer killing property.

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