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The centrosome is a crucial, membraneless organelle that orchestrates the assembly and organization of microtubules. During cell division, the centrosome forms the spindle apparatus that segregates chromosomes into daughter cells. Additionally, the centrosome participates in cellular organization and polarity by anchoring microtubules and directing their growth towards specific cellular structures, thereby regulating cell shape, movement, and intracellular transport. Dysfunction of the centrosome can lead to aberrant cell division, cytoskeletal defects, and ultimately contribute to various diseases, including cancer and developmental disorders.
Our Aim: (1) To understand how centrosomes are positioned to perform varied cell type specific functions during development, (2) How centrosomes modulate their microtubule nucleating capacity through the cell cycle, (3) Determine how the disfunction of these two critically important regulatory pathways leads to disease including Cancer, Microcephaly and Male Sterility.
Approach: Our lab uses modern genetic approaches, live cell microscopy, and in vitro reconsitution to answer these questions.
Ongoing Projects:
Ongoing Projects:
Mechanisms of Asymmetric Cell Division
Asymmetric cell division occurs when cellular contents, such as organelles, proteins, and genetic material, are distributed unequally between the daughter cells. This process is vital for generating cellular diversity and maintaining tissue homeostasis in multicellular organisms. In stem cells, the two centrosomes are asymmetric in both composition and function, this centrosome asymmetry is crucial for the asymmetric divisions due to differential ability to nucleate microtubules.
Open questions we are investigating relevant to centrosome asymmetry in asymmetric cell division:
1. How is centrosome microtubule organizing activity regulated?
2. How are centrosomes positioned to ensure the asymmetric distribution of cellular contents?
3. What is the consequence of centrosome dysregulation in stem cells?
Molecular Control of Spermiogenesis
Approximately 10% of American couples are deemed infertile. Male factors account for 30-50% of these cases. The centrosome (Green) is key to spermiogenesis linking the head (Blue) to the tail (Red). We recently showed that centrosome proteins are also critical for regulating the manchette which shapes the sperm head, as well as a sperm individualization which is a crucial step in sperm production.
Open questions we are investigating relevant to centrosome function in spermiogenesis:
1. Where and when are microtubule nucleated during spermiogenesis?
2. How do testes specific isoforms of centrosome proteins differ in function to somatic cells?
3. How is material transported to different regions of the sperm?
Other Interests:
Centriole Ultrastructure
Centriole Ultrastructure
Developmental Biology
Developmental Biology
Gut Structure and Function
Gut Structure and Function
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