Kundu Lab

Our laboratory studies the how cells respond to metabolic stress, with particular interests in the role of autophagy-related proteins in coordinating that cellular response and the impact of somatic mitochondrial DNA mutations on cancer pathogenesis and progression. We approach questions in lab at multiple levels, beginning with the whole organism and drilling down into that organism’s molecular elements.

Another major project in our laboratory centers on the role of somatic mitochondrial DNA mutations in the pathogenesis of cancer. Understanding the role of mtDNA mutations and their role in cancer pathogenesis and progression has been somewhat limited by the inability to effectively engineer these mtDNA mutations and study their effects. Up until recently, the study of mtDNA research relied largely on the generation of cybrids, a technique that involves taking the cytoplasm from one cell and fusing it with a nucleus of another. 

Our laboratory has used a different approach to investigate the role of somatic mtDNA mutations in cancer. First, we use the mtDNA mutator mouse model in which genetic mutations accumulate over time as the mitochondria replicate. We isolate bone marrow from the wild type, heterozygous, and homozygous mtDNA mutator models to decipher the different burdens of mutations. From there, we introduce oncogenes and monitor tumor development to determine the role of somatic mtDNA in the development of cancer. 

We are also working with computational biology experts to develop a pipeline to identify mtDNA mutations in tumor cells by documenting and characterizing the mutations that occur in various types of tumors. As part of this endeavor, we have developed new methods to identify mtDNA mutations and have shown that somatic mtDNA mutations accumulate to a significant enough level to profoundly influence the cell state.