Jadranka Loncarek, Ph.D.
Jadranka  Loncarek, Ph.D.
Investigator

Dr. Loncarek studies the fundamentals of centrosome biology and cellular processes associated with their activity. She aims to unravel the regulatory pathways that control centrosome number in normal and pathological conditions such as human tumors. The Loncarek lab uses various biochemical and cell biology methods and combines them with high resolution live-cell imaging, super resolution and electron microscopy.

Areas of Expertise
1) cell biology, 2) centrosome, 3) light microscopy, 4) electron microscopy

Contact Info

Jadranka Loncarek, Ph.D.

Center for Cancer Research
National Cancer Institute

Building 560, Room 12-90
Frederick, MD 21702
301-846-1059

The aim of our studies is to understand how the proper number of the centrosomes is maintained in proliferating cells.

A centrosome is a minute cellular organelle present in only two copies per typical cycling animal cell. It is built of stable core structure - a centriole- and amorphous cloud of pericentriolar material. A centrosome organizes cytoplasmic microtubule cytoskeleton during interphase. During mitosis, two centrosomes organize poles of mitotic spindle, facilitating proper chromosome alignment and their segregation between two daughter cells. Thus, the centrosomes stabilize the genome forming a bipolar mitotic spindle. Centrosomes also transform into basal bodies to nucleate the formation of primary cilia. Primary cilium is a sensory organelle indispensable for signaling during development and for the normal functioning of many organs. Centrosome is a versatile and dynamic organelle whose function amends to the cell cycle conditions.

Structural and numerical centrosome abnormalities are the hallmark of most tumors, especially aggressive ones. Likewise, the defects in primary cilium formation have been implicated in numerous human diseases. Understanding the molecular mechanisms that regulate centrosome number and function is a paramount for understanding centrosome- related diseases.

A typical dividing human cell has two centrosomes, containing single or duplicated centriole, depending on the phase of the cell cycle. Each centriole is a nine-fold barrel-shaped structure made of nine microtubule triplets and accompanying proteins. By a, yet unknown mechanism, centrioles organize pericentriolar material and, as a result, the number of centrioles determine the number of centrosomes in the cell. The cell strictly controls the number of centrosomes by coupling the centriole cycle with other cell cycle events, so that each preexisting centriole duplicate precisely once per cell cycle and segregate evenly during mitosis. Centriole amplification has been documented to correlate with a loss of tumor suppressor proteins, with oncogenic virus infections, DNA damage, or with prolonged interphase induced by chemical inhibitors. Molecular mechanisms behind these pathological conditions promoting centriole amplification are poorly understood because the basic knowledge about how is centriole cycle regulated during normal cell cycle are still lacking.

A general question and a long-term goal of our research is to understand how centriole cycle is coordinated with other cell cycle events and how is spatially regulated within a centrosome. We study molecular mechanisms that regulate initiation of centriole formation, their maturation, disengagement, and segregation in various normal and transformed mammalian (mostly human) cells in the culture. Methodologically, we use a multipronged experimental approach and combine state of the art molecular biochemical methods with live- and fixed- high-end microscopy techniques, to reach our research goals.

Job openings: To inquire about potential open positions in the lab, please e-mail a cover letter and CV to Dr Loncarek.

Scientific Focus Areas:
Cancer Biology, Cell Biology
Selected Key Publications
  1. 1. Kong D, Farmer V, Shukla A, James J, Gruskin R, Kiriyama S, Loncarek J.
    J Cell Biol. 206(7): 855-65, 2014. [ Journal Article ]
  2. Kim TS, Park JE, Shukla A, Choi S, Murugan RN, Lee JH, Ahn M, Rhee K, Bang JK, Kim BY, Loncarek J, Erikson RL, Lee KS.
    Proc Natl Acad Sci U S A. 110(50): E4849-57, 2013. [ Journal Article ]
  3. Loncarek J, Hergert P, Khodjakov A
    Curr Biol. 20(14): 1277-82, 2010. [ Journal Article ]
  4. Loncarek J, Khodjakov A
    Mol Cells. 27(2): 135-42, 2009. [ Journal Article ]
  5. Loncarek J, Hergert P, Magidson V, Khodjakov A
    Nat Cell Biol. 10(3): 322-8, 2008. [ Journal Article ]

Dr. Jadranka Loncarek has joined the Laboratory of Protein Dynamics and Signaling, Dr. Allan M. Weissman, Chief, as an NIH Earl Stadtman Tenure Track Investigator. She obtained her Ph.D. from the Faculty of Sciences at Zagreb University, Croatia, in cell and molecular biology. She completed her postdoctoral training in the laboratory of Dr. Alexey Khodjakov at Wadsworth Center, Albany, New York, where she studied the mechanisms of centriole duplication and mitotic spindle formation. Her current research focuses on elucidating the molecular mechanism of centrosome biogenesis and their function, with particular attention on numerical control of centrosome formation in non-transformed and cancerous human cells.

Name Position
Veronica Farmer M.S. Postbaccalaureate Fellow
Dong Kong Postdoctoral Fellow (Visiting)
Sett Naing Summer Student
Vignesh Rajasekaran Summer Student
Meena Sharma Predoctoral Fellow
Anil Shukla Postdoctoral Fellow (Visiting)
Sheetal Uppal Postdoctoral Fellow (Visiting)

Research

The aim of our studies is to understand how the proper number of the centrosomes is maintained in proliferating cells.

A centrosome is a minute cellular organelle present in only two copies per typical cycling animal cell. It is built of stable core structure - a centriole- and amorphous cloud of pericentriolar material. A centrosome organizes cytoplasmic microtubule cytoskeleton during interphase. During mitosis, two centrosomes organize poles of mitotic spindle, facilitating proper chromosome alignment and their segregation between two daughter cells. Thus, the centrosomes stabilize the genome forming a bipolar mitotic spindle. Centrosomes also transform into basal bodies to nucleate the formation of primary cilia. Primary cilium is a sensory organelle indispensable for signaling during development and for the normal functioning of many organs. Centrosome is a versatile and dynamic organelle whose function amends to the cell cycle conditions.

Structural and numerical centrosome abnormalities are the hallmark of most tumors, especially aggressive ones. Likewise, the defects in primary cilium formation have been implicated in numerous human diseases. Understanding the molecular mechanisms that regulate centrosome number and function is a paramount for understanding centrosome- related diseases.

A typical dividing human cell has two centrosomes, containing single or duplicated centriole, depending on the phase of the cell cycle. Each centriole is a nine-fold barrel-shaped structure made of nine microtubule triplets and accompanying proteins. By a, yet unknown mechanism, centrioles organize pericentriolar material and, as a result, the number of centrioles determine the number of centrosomes in the cell. The cell strictly controls the number of centrosomes by coupling the centriole cycle with other cell cycle events, so that each preexisting centriole duplicate precisely once per cell cycle and segregate evenly during mitosis. Centriole amplification has been documented to correlate with a loss of tumor suppressor proteins, with oncogenic virus infections, DNA damage, or with prolonged interphase induced by chemical inhibitors. Molecular mechanisms behind these pathological conditions promoting centriole amplification are poorly understood because the basic knowledge about how is centriole cycle regulated during normal cell cycle are still lacking.

A general question and a long-term goal of our research is to understand how centriole cycle is coordinated with other cell cycle events and how is spatially regulated within a centrosome. We study molecular mechanisms that regulate initiation of centriole formation, their maturation, disengagement, and segregation in various normal and transformed mammalian (mostly human) cells in the culture. Methodologically, we use a multipronged experimental approach and combine state of the art molecular biochemical methods with live- and fixed- high-end microscopy techniques, to reach our research goals.

Job openings: To inquire about potential open positions in the lab, please e-mail a cover letter and CV to Dr Loncarek.

Scientific Focus Areas:
Cancer Biology, Cell Biology

Publications

Selected Key Publications
  1. 1. Kong D, Farmer V, Shukla A, James J, Gruskin R, Kiriyama S, Loncarek J.
    J Cell Biol. 206(7): 855-65, 2014. [ Journal Article ]
  2. Kim TS, Park JE, Shukla A, Choi S, Murugan RN, Lee JH, Ahn M, Rhee K, Bang JK, Kim BY, Loncarek J, Erikson RL, Lee KS.
    Proc Natl Acad Sci U S A. 110(50): E4849-57, 2013. [ Journal Article ]
  3. Loncarek J, Hergert P, Khodjakov A
    Curr Biol. 20(14): 1277-82, 2010. [ Journal Article ]
  4. Loncarek J, Khodjakov A
    Mol Cells. 27(2): 135-42, 2009. [ Journal Article ]
  5. Loncarek J, Hergert P, Magidson V, Khodjakov A
    Nat Cell Biol. 10(3): 322-8, 2008. [ Journal Article ]

Biography

Dr. Jadranka Loncarek has joined the Laboratory of Protein Dynamics and Signaling, Dr. Allan M. Weissman, Chief, as an NIH Earl Stadtman Tenure Track Investigator. She obtained her Ph.D. from the Faculty of Sciences at Zagreb University, Croatia, in cell and molecular biology. She completed her postdoctoral training in the laboratory of Dr. Alexey Khodjakov at Wadsworth Center, Albany, New York, where she studied the mechanisms of centriole duplication and mitotic spindle formation. Her current research focuses on elucidating the molecular mechanism of centrosome biogenesis and their function, with particular attention on numerical control of centrosome formation in non-transformed and cancerous human cells.

Team

Name Position
Veronica Farmer M.S. Postbaccalaureate Fellow
Dong Kong Postdoctoral Fellow (Visiting)
Sett Naing Summer Student
Vignesh Rajasekaran Summer Student
Meena Sharma Predoctoral Fellow
Anil Shukla Postdoctoral Fellow (Visiting)
Sheetal Uppal Postdoctoral Fellow (Visiting)