Dr. Kirill Kiselyov

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
V. Oke
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
G. Hatfull
R. Hendrix
J. Lawrence
V. Oke
J. Pipas
M. Popa
I. Campbell
R.L. Duda
S. Godfrey

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Kiselyov

TRP Ion Channels; Human Genetic Diseases Caused by Mutations in TRP Channels

Assistant Professor

Dr. Kiselyov received his Ph.D. in 1997 with Galina Mozhayeva at the Institute of Cytology, St. Petersburg, Russia, performed his postdoctoral studies with Shmuel Muallem at the University of Texas Southwestern, and joined the Department in 2003.

Currently, Dr. Kiselyov is accepting graduate students in his laboratory. Dr. Kiselyov is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Kirill Kiselyov

Fig. 1. An electron microscopic zoom-in on human skin fibroblasts from control individual and from an MLIV patient. Treating cells with a lysosomal H⁺ uptake inhibitor nigericin decreases the numbers of lipid inclusions characteristic for MLIV.

Cells take up material from the extracellular space and degrade it for energy and for building material. This process is called endocytosis. The cellular digestive tract is somewhat similar to ours, as it is comprised of a series of compartments that sort, digest and absorb food. The final degradation of the endocytosed material occurs in lysosomes, vesicular organelles filled with digestive enzymes. The lysosomal digestive activity depends on acidic conditions, which are controlled by a system of ion channels and transporters present in lysosomal membranes. Mutations in the genes coding for the lysosomal digestive enzymes and transport molecules render cells unable to properly handle food and lead to buildup of undigested material in lysosomes. Such conditions, called lysosomal storage diseases, are rare, but deadly as they result in severe developmental delays, motor and cognitive disabilities and abbreviated lifespan. Analysis of the proteins that are mutated in lysosomal storage diseases leads to better understanding of lysosomal digestive machinery.

The main research project in our lab is focused on pathogenesis of lysosomal storage disease called mucolipidosis type IV (MLIV). This is a rare genetic disorder caused by mutations in a gene coding for the lysosomal ion channel mucolipin 1 (TRPML1). At present, the function of TRPML1 in lysosomes is being discussed and may involve regulation of the transfer of endocytosed material between lysosomes and upstream organelles, or it may directly affect the activity of lysosomal digestive enzymes. The data obtained by our lab in collaboration with Dr. Muallem's group in UT Southwestern indicate that TRPML1 may regulate lysosomal acidity by leaking H+ through the lysosomal membrane. The H+ leak works as a safety valve mechanism that prevents lysosomal overacidification. We suggest that in the absence of such leak, lysosomes become too acidic and do not work properly. Accordingly, we found that adjusting lysosomal acidity may alleviate the cellular phenotype of MLIV.

Fig. 2. Mitochondria in control (top) and MLIV-affected human skin fibroblasts (bottom) stained with a mitochondrial specific fluorescent dye.

Most of lysosomal storage diseases severely affect on brain function, which is attributed to neuronal death. The mechanisms of cell death in lysosomal storage diseases are not well understood, although better understanding of cell death in lysosomal storage diseases may lead to formulating novel interventions into the neurodegenerative aspects of lysosomal storage diseases.

The second project in our lab is aimed to uncover cell death pathways that lead to degenerative processes in lysosomal storage diseases. In addition to their role in endocytosis, lysosomes also participate in autophagy, a process of digestion by cells of their own effete organelles. We suggest that suppression of lysosomal function in lysosomal storage diseases affect autophagy of effete mitochondria and results in accumulation of fragmented dysfunctional mitochondria. In addition to their role in energy production, mitochondria are actively involved in buffering cytoplasmic calcium, an excess of which is well known to cause apoptosis. A decrease in calcium buffering by mitochondria in cells affected by lysosomal storage diseases makes the cells vulnerable to pro-apoptotic effects of calcium, which may explain cell death in lysosomal storage diseases.

Publication Archive
29 Citations
29 Abstracts
21 PDFs

Recent Publications of Kirill Kiselyov

Kim, H.J., Q. Li, S. Tjon-Kon-Sang, I. So, K. Kiselyov, and S. Muallem (2007) Gain-of-function mutation in TRPML3 causes the mouse varitint-waddler phenotype. J. Biol. Chem. 0:

Vergarajauregui, S., R. Oberdick, K. Kiselyov, and R. Puertollano (2007) Mucolipin-1 channel activity is regulated by protein kinase A mediated phosphorylation. Biochem. J. 0:

Worley, P.F., W. Zeng, G. Huang, J.Y. Kim, D.M. Shin, M.S. Kim, J.P. Yuan, K. Kiselyov, and S. Muallem (2007) Homer proteins in Ca²⁺ signaling by excitable and non-excitable cells. Cell Calcium 42:363-371

Kiselyov, K., J.J. .J.r. Jennigs, Y. Rbaibi, and C.T. Chu (2007) Autophagy, mitochondria and cell death in lysosomal storage diseases. Autophagy 3:259-262

Kiselyov, K., A. Soyombo, and S. Muallem (2006) TRPpathies. J. Physiol. 578:641-653

Kiselyov, K., X. Wang, D.M. Shin, W. Zang, and S. Muallem (2006) Calcium signaling complexes in microdomains of polarized secretory cells. Cell Calcium 40:451-459

Jennings, J.J., J.r., J.H. Zhu, Y. Rbaibi, X. Luo, C.T. Chu, and K. Kiselyov (2006) Mitochondrial aberrations in mucolipidosis type IV. J. Biol. Chem. 281:39041-39050 (PDF Reprint: 753 kb)

Kim, J.Y., W. Zeng, K. Kiselyov, J.P. Yuan, M.H. Dehoff, K. Mikoshiba, P.F. Worely, and S. Muallem (2006) Homer 1 mediates store- and IP3Rs- dependent translocation and retrieval of TRPC3 to the plasma membrane. J. Biol. Chem. 281:32540-32549 (PDF Reprint: 2.2 MB)

Soyombo, A.A., S. Tjon-Kon-Sang, Y. Rbaibi, E. Bashllari, J. Bisceglia, S. Muallem, and K. Kiselyov (2006) TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity. J. Biol. Chem. 281:7294-7301 (PDF Reprint: 799 kb)

Kiselyov, K., J. Chen, Y. Rbaibi, D. Oberdick, S. Tjon-Kon-Sang, N. Shcheynikov, S. Muallem, and A. Soyombo (2005) TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage. J. Biol. Chem. 280:43218-43223 (PDF Reprint: 1.3 MB)

Kiselyov, K., J.Y. Kim, W. Zeng, and S. Muallem (2005) Protein-protein interaction and functionTRPC channels. Pflug. Arch. Eur. J Phy. 451:116-124 (PDF Reprint: 343 kb)

van Rossum, D.B., R.L. Patterson, K. Kiselyov, D. Boehning, R.K. Barrow, D.L. Gill, and S.H. Snyder (2004) Agonist-induced Ca²⁺ entry determined by inositol 1,4,5-trisphosphate recognition. Proc. Natl. Acad. Sci., USA 101:2323-2327 (PDF Reprint: 597 kb)

Kiselyov, K., D.M. Shin, and S. Muallem (2003) Signalling specificity in GPCR-dependent Ca2+ signalling. Cell. Signal. 15:243-253 (PDF Reprint: 565 kb)

Yuan, J.P., K. Kiselyov, D.M. Shin, J. Chen, N. Shcheynikov, S.H. Kang, M.H. Dehoff, M.K. Schwarz, P.H. Seeburg, S. Muallem, and P.F. Worley (2003) Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114:777-789 (PDF Reprint: 582 kb)

Choi, J.Y., D. Muallem, K. Kiselyov, M.G. Lee, P.J. Thomas, and S. Muallem (2001) Aberrant CFTR-dependent HCO₃^- transport in mutations associated with cystic fibrosis. Nature 410:94-97 (PDF Reprint: 328 kb)

How to Contact Kirill Kiselyov

US Mail
University of Pittsburgh
Department of Biological Sciences
215A Clapp Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-4317
Lab : (412) 624-4305
FAX : (412) 624-4759
Email : kiselyov+@pitt.edu
Web :

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