Molecular Physiology and Biophysics

Background

Research Description

The Stumpff lab utilizes a combination of cutting edge quantitative cell biology and single molecule approaches to investigate the molecular mechanisms controlling cell division and how they relate to human disease.

Cell division, in its simplest terms, is the process by which one cell becomes two. Cellular proliferation is necessary for the survival and development of all organisms, and a key objective during the division process is to equally segregate one complete set of replicated chromosomes to each daughter cell. This step is dependent on the microtubule-based mitotic spindle, which acts to capture, align and then partition replicated chromosome pairs. Mitotic spindle function must be tightly regulated to prevent chromosome segregation errors and the production of aneuploid cells, i.e. cells with the wrong number of chromosomes. Aneuploidy is a hallmark of both solid tumor and blood cancer cells, is implicated in the initiation and development of cancer, is a leading cause of human miscarriages and is the cause of monosomy and trisomy syndromes. Thus, elucidating the mechanisms underlying the organization and movement of chromosomes within the mitotic spindle is an important step towards a molecular understanding of a wide range of human health disorders.

We are currently investigating several fundamental questions related to understanding the mechanisms controlling mitotic chromosome organization and movement:

1. How do kinesin motor proteins contribute to the spatial and temporal control of chromosome movements and how do defects in these mechanisms contribute to disease?

2. What are the mechanisms that regulate the mechanochemical properties of mitotic kinesins?

3. How does the spatial control of mitotic chromosome movements contribute to the accurate segregation of the genome and its stability?

4. Can proteins involved in controlling mitotic chromosome movements be exploited as anti-cancer targets?

Faculty Highlighted Publications

Fonseca CL, Malaby HLH, Sepaniac LA, Martin W, Byers C, Czechanski A, Messinger D, Tang ME, Ohi R, Reinholdt LG, and Stumpff J (2019). Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase. JCB 218: 1148-1163, PMCID: PMC6446859 (*co-corresponding authors)

Malaby HLH, Dumas M, Ohi R, and Stumpff J (2019). Kinesin binding protein ensures accurate chromosome segregation by buffering Kif18A and Kif15. JCB 218: 1218-1234, PMCID: PMC6446846 (*co-corresponding authors).

Malaby HLH, Lessard DV, Berger CL, and Stumpff J (2019).  KIF18A’s neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle. LSA. 2019, 2:e201800169. PMID: 30655363

Muretta JM*, Reddy BJN*, Scarbelli G*, Thompson AF*, Jariwala S, Major J, Venere M, Rich JN, Willard B, Thomas DD, Stumpff J, Grant BJ, Gross SP, and Rosenfeld SS (2018). A post-translational modification of Eg5 that enhances its mechano-chemical coupling and alters its mitotic function. PNAS. 115:E1779-E1788  (*equal contribution) 

All J. Stumpff Publications >>