Research Opportunities 

  1. Undergraduate Researchers :If you are interested in learning about Cancer and want to get hands-on experience using model organisms to understand gene function ,contact me regarding available positions.
  2. Graduate Research Assistants: The department of Biology at University of Dayton offers a graduate program in Biomedical Science, if you are interested in pursuing a Masters/Ph D Degree, and you are interested in  working with me, contact me.
Madhuri Kango-Singh

  Research Interests 

  1. Regulation of Growth Control during Development and Cancer 

  2. Regulation of Organ Growth      

 

 



Regulation of Growth Control during Development and Cancer

            How do cells know when to stop proliferating during development? How do cancer cells acquire  the ability to proliferate incessantly and evade apoptosis? These questions have intrigued cancer biologists for a long time. Understanding the molecular mechanisms that instruct cells to cease proliferation at the end of animal development or in maintaining homeostasis in adult life will shed light on the underlying molecular genetic mechanisms that regulate growth during development or are disrupted in diseases like cancer.

           Recently, we (and others) have identified a new network of tumor suppressor genes- called the Hippo pathway that functions to regulate proliferation and survival of cells. The Hippo pathway has been implicated in (a) p53-dependent apoptotic response to ionizing radiation in flies, (b) pathogenesis of several human cancers e.g., ovarian, lung, colon cancer and (c) contact inhibition in mammalian tissue culture cells. These developments unleash exciting possibilities for studying the role of Hippo pathway in diseases linked to defects in proliferation/apoptosis or both.

 





         My long-term interest is to understand and characterize the pathways that control tumor progression and metastasis at the molecular level. Metastasis is the primary cause of death for most cancer patients. Tumor progression and metastasis are linked to changes in cell polarity, adhesion and motility in addition to loss of proliferation control. Understanding the molecular mechanisms that regulate cell invasion is the first step in this quest because cell invasion marks the beginning of tumor progression and metastasis. So far we have a poor understanding of the molecular mechanisms that trigger cells to leave the epithelium during normal development or cell invasion.

         Sophisticated genetics in Drosophila has proven powerful for molecular dissection of cancer pathways, and to model metastasis. Thus, my rationale is to exploit the conservation of Drosophila molecules and cellular processes to obtain insights into human tumor cell invasion. To do so, we have developed a simple genetic model to study the mechanisms of tumor cell invasion in the fruit fly Drosophila melanogaster.

Currently work in my laboratory focuses on two main themes:

  I. Understanding the role of Hippo signaling during development and in cancer by     

      (a) Identification of a role of Hippo signaling in tumor progression, and

      (b) Identification of additional components of the Hippo pathway to understand  its role during development and in cancer.

  II. Identification of genes involved in tumor invasion using sophisticated genetic screens in Drosophila.




Regulation of Organ Growth
 

         A sequence of developmental steps is responsible for the precise regulation of processes that culminate in the normal development of the eye. In humans, the important eye development phase is programmed to take place in the first 3 months of pregnancy. Failure of any of the early eye development stages may cause anophthalmia (absent eye) and/or microphthalmia (small eye).  Model organisms have proven informative in furthering our understanding of the genetic and biochemical pathways involved in the genesis of complex disorders. The basic genetic machinery required for visual system development is conserved. For example, PAX-6/ey is essential for eye differentiation throughout the animal kingdom. Thus insufficient growth of the eye primordium may be responsible for the growth defects observed in microphthalmia using Drosophila as a model system. Amongst the many growth regulatory pathways, the recently identified Hippo pathway has emerged as the size-regulating pathway. This pathway is conserved functionally from flies to humans, and is composed of several tumor suppressor genes and oncogenes. Remarkably, inactivation of the Hippo pathway results in massive tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis. Further, activation of the Hippo pathway by over-expression leads to induction of cell death resulting in reduced organ size. Thus during normal development, this pathway plays an important role in limiting organ sizes. Currently, we are testing if Hippo signaling activity is altered in Drosophila mutants with reduced or ‘eye-less” phenotypes, and if inactivation of Hippo pathway can rescue/restore the eye size of these mutants.

 
a;tThe small-eye presentation characteristic of microphthalmia  is phenocopied by mutations in several fly genes e.g., ey2.