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Research at Mass General
Massachusetts General HospitalCutaneous Biology Research CenterBuilding 149, 13th StreetCharlestown, MA 02129617 726-6691Email:email@example.com
Since my years as a Harvard faculty member, I have focused a sustained effort toward cancer biology, and my initial most significant contribution was the first to discover that pro-survival pathway activation is directly associated with p53-dependent genotoxic responses in cancer cells, and have provided a unique and significant contribution in this area.
As an Assistant and then as an Associate Professor at the BIDMC and the MGH/Harvard Medical School, I pursued my major interest in how tumor suppressor p53-mediated transcriptional regulation influences cell fate decisions: live or die.
Based on my contribution concerning the dark side of p53 in cancer therapeutics that wt-p53 can function as a guardian of cancer genome for their survival against therapeutic stress, I have established close collaborations with the Broad Institute utilizing their technological, computational and chemical biological tools under their Chemical Genetics Platform.
Together with Broad scientists, I have identified several promising small molecules with anti-cancer activity through the activation of tumor suppressor p53 apoptotic pathway. Specifically, we have identified a small molecule to induce apoptosis selectively in cells having a cancer genotype by targeting a non-oncogene co-dependency acquired by the expression of the cancer genotype in response to transformation-induced oxidative stress.
This highlights a novel strategy for cancer therapy that preferentially eradicates cancer cells by targeting the ROS stress-response pathway. My experience in this area has played a major role in the development of a Chemical Genetics Core facility at CBRC in collaboration with the Broad Institute. My group now possesses considerable experience in systematic small molecule technologies. I will continue to assist with the design, validation, execution and interpretation of investigator initiated chemical genetic screens.
Aditi U Gurkar
So Young Hwang
Hyung Gu Kim
Kyoung Wan Yoon
Han, J.A., Kim, J.-I., Hwang, D.H., Ballou, L.R., Mahale, A., Aaronson, A.A., and Lee, S.W. p53-mediated induction of Cox-2 counteracts p53- or genotoxic stress-mediated apoptosis.EMBO J.21: 5635-5644, 2002.
Macip, S., Igarashi, M., Fang, L., Lee, S.W., and Aaronson, S.A. Inhibition of p21Waf1/Cip1/Sdi1-mediated ROS accumulation can rescue p21-induced senescence.EMBO J.21: 2180- 2188, 2002.Wulf, G.M., Loiu, Y.-C., Ryo, A., Lee, S.W., and Lu, K.P. Role of Pin1 in regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage. J. Biol. Chem.277: 47976-47979, 2002.
Ryo, A., Wulf, G.M., Loiu, Y.-C., Lee, S.W., and Lu, K.P. Pin1 is an E2F target gene essential for Neu/Ras-induced transformation of mammary epithelial cells.Mol. Cell. Biol.22:5281-5295, 2002.Ohtsuka, T., Ryu, H., Minamishima, Y.A., Ryo, A., and Lee, S.W. Modulation of p53 and p73 levels by cyclin G: implication of a negative feedback regulation.Oncogene, 22: 1678-1687, 2003.
Ongusaha, P.P., Ouchi, T., Kim, K.T., Nytko, E., Kwak, J.C., Deng, C.-X., and Lee, S.W. BRCA1 shifts p53-mediated cellular outcomes toward irreversible growth arrest.Oncogene, 22: 3749-3758, 2003. Ongusaha, P., Kim, J-I., Fang, L. Wong, T.W., Yancopoulos, G.D., Aaronson, A.A., and Lee, S.W. p53 induction and activation of DDR1 kinase counteract p53-mediate apoptosis and influence p53 regulation through a positive feedback loop.EMBO J.22: 1289-1301, 2003.
Aglipay, J.A., Lee, S.W., Okada, S., Kwak, J.C., Qin, J., and Ouchi, T. A Member of the PYRIN Family, IFI16, is a Novel BRCA1-associated Protein Involved in the p53-mediated Apoptosis Pathway.Oncogene 22: 8931-8938, 2003.Kwak, J.C., Ongusaha, P.P., Ouchi, T., and Lee, S.W. IFI16 as a negative regulator in the regulation of p53 and p21Waf1.J. Biol. Chem.278: 40899-40904, 2003.
Macip, S., Igarashi, M., Berggren, P., Yu, J., Lee, S.W., and Aaronson, S.A. Influence of induced ROS in determining p53-mediated cell fate decisions.Mol. Cell. Biol.23: 8576-8585, 2003.Ohtsuka, T., Jensen, M.R., Kim, H.G., and Lee, S.W. The negative role of cyclin G in ATM-dependent p53 activation.Oncogene 23: 5405-5408, 2004.
Fujiuchi N., Aglipay J.A. Ohtsuka, T., Machara, N., Sahin, F., Su, G.H., Lee, S.W., and Ouchi, T. Requirement of IFI16 for the maximal activation of p53 induced by ionizing radiation.J. Biol. Chem. 279: 20339-20344, 2004.
Ouchi M., Fujiuchi N., Ongusaha P.P., Minamishima, Y.A., Sasai K., Katayama, H., Deng, C., Sen, S., Lee, S.W., and Ouchi, T. Requirement of BRCA1 phosphorylation by aurora-A for entry into mitosis.J. Biol. Chem. 279: 19643-19648, 2004.Ohtsuka, T., Ryu, H., Minamishima, Y.A., Macip, S., Sagara, J., Aaronson, S.A., and Lee, S.W. ASC functions as an adaptor for Bax and regulates a p53-Bax mitochondrial pathway of apoptosis.Nature Cell Biol.6: 121-128, 2004.
Kim, K.T., Ongusaha, P.P., Hong, Y.-K., Kurdistani, S.K., Nakamura, M., Lu, K.P. and Lee, S.W. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint. J. Biol. Chem. 279: 38597-38602, 2004.Ongusaha, P.P., Kwak, J.C., Zwible, A.J., Macip, S., Higashiyama, S., Taniguchi, N., Fang, L., and Lee, S.W. Heparin-binding epidermal growth factor-like growth factor HB-EGF is a potent inducer of tumor growth and angiogenesis.Cancer Res.64: 5283-5290, 2004.
Aglipay, J.A., Lee, S.W., and Ouchi, T. ATM Activation by Ionizing Radiation Requires BRCA1-associated BAT1.Nature Cell Biology, Accepted.lism, Submitted, 2005.
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Cutaneous Biology Research Center
Directions to Charlestown Navy Yard MGH East - Building 149
From Storrow Drive
From the end of Storrow Drive (Leverett Circle) keep to the far right and take a sharp right (do not go up the ramp), and continue beneath the underpass one quarter mile to the light.
Turn left onto Causeway street under the elevated subway tracks. The Fleet Center will be on your left, the North Station T station on your right.
One block past the Garden, turn left on to N. Washington Street, passing over the Charlestown Bridge.
At the first light after the bridge, take a right. Go through three traffic control lights.
At the fourth light, turn right into Navy Yard (Gate 5 - 13th Street). To park, take first left onto Fifth Avenue. Building 149 is one block on the right.
The parking garage entrance is on the right about half way down the block.
Take the Mass Pike (I-90) to I-93 North (Exit 24B)
Take the Storrow Drive Exit (Exit 26)Stay in the left lane once getting on the exit ramp. Follow signs for North Station/Leverett Circle Go through 1 light and take left at the 2nd light (almost immediately after the first)
Get immediately into the right lane
Take a right at the light onto Route 28N
The Museum of Science will be on your left
Take a right at the 3rd light (there is a sign at the corner for Charlestown)
Go over the bridge and get in the right lane (City Square)
Take your 1st right and get into the left lane
Turn left at the 2nd light (immediately before Charlestown Bridge, at City Square) onto Chelsea Street (If you go over bridge, you've gone too far).
Go through three traffic control lights
At the 4th light, turn right into the Navy Yard (Gate 5 - 13th Street).
To park, take first left onto Fifth Avenue. Parking Garage entrance is on the right above half way down the block. Building 149 is one block on the right once you turn into Gate 5. Building 149 is also connected to the parking garage.
Take Exit 28 (Charlestown/Sullivan Square).
At the end of the exit where the read forks stay to the right and proceed past the bus terminal to the rotary at Sullivan Square.
Go halfway around the rotary towards Charlestown (the Schrafts building with a large American flag on top of it will be on your left).
Cross the railroad tracks and take a left at the fire station onto Medford Street.
At the end of Medford street turn left onto Chelsea Street and make an immediate right into the Navy Yard.
The MGH East Research Building (Bldg. 149) will be on the right and is connected to the parking garage by overhead walkways.
Direct the driver to the MGH East, Building 149 in the Charlestown Navy Yard.
The CBRC is on the 3rd Floor of Building 149.By Public Transportation & the MGH/Partners Shuttle
Take the T (Green Line) to North Station
Take the MGH/Partners Shuttle bus to the Charlestown Navy Yard MGH East Research Building (Building 149).
The CBRC is on the 3rd Floor.
The MGH/Partners Shuttle bus leaves MGH on Blossom Street and stops at North Station on Canal Street by the Green Line T stop. The shuttle goes every 15 minutes during working hours. (Less often on the weekends and holidays).
To get to the CBRC, take the first set of elevators to the left of the main entrance by the Security Desk to the third floor. You may need to check in with security on the main level of Building 149.
From the elevator, exit to the East to the CBRC offices, or in the opposite direction for the laboratories.
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