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Luca Busino, Ph.D.
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Associate Professor of Cancer Biology
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Department: Cancer Biology
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Graduate Group Affiliations
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Contact information
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421 Curie Blvd
36 705 BRB II/III
Philadelphia, PA 19104-6160
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36 705 BRB II/III
Philadelphia, PA 19104-6160
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Lab: 215-746-2569
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Email:
businol@upenn.edu
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businol@upenn.edu
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Education:
21 9 B.S. 22 (Medical Biotechnology) c
3b Università di Napoli, Federico II, 1999.
21 9 M.S. 22 (Medical Biotechnology) c
3b Università di Napoli, Federico II, 2001.
21 a Ph.D. 22 (Experimental Oncology) c
37 European Institute of Oncology, 2008.
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Permanent link21 9 B.S. 22 (Medical Biotechnology) c
3b Università di Napoli, Federico II, 1999.
21 9 M.S. 22 (Medical Biotechnology) c
3b Università di Napoli, Federico II, 2001.
21 a Ph.D. 22 (Experimental Oncology) c
37 European Institute of Oncology, 2008.
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201 My laboratory studies the mechanisms by which the ubiquitin-proteasome system (UPS) controls cell proliferation and how alterations in these processes contribute to tumor initiation and maintenance. Misregulation of protein degradation pathways is often observed in cancer cells. Integrating the study of cellular signals with the molecular mechanisms by which ubiquitin ligases target substrates will advance our knowledge of cancer biology and will provide novel avenues for development of therapeutics.
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11e Areas of interest within the laboratory include, but are not limited to: (i) Signaling Pathways (such as those related to the cell division cycle, DNA damage response, circadian clock, and NFkB signaling) and (ii) Identification of small molecules to target ubiquitin ligases.
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19 Busino Lab
20f Hematological malignancies are tumors that affect blood, bone marrow and lymph nodes. Taken together, hematological malignancies account for approximately 10% of new cancer diagnoses in the United States. Drugs that target the UPS, such as thalidomide and bortezomib, improve survival, underlining the effectiveness of targeting the UPS, but resistance to these therapies eventually develops. Therefore, the identification of novel UPS enzymes that could serve as targets is crucial for the development of therapeutics.
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40 My laboratory focuses on two main research areas:
5d (i) Functional discoveries in the area of ubiquitin system and hematologic diseases.
13f This research area aims to characterize the molecular functions of cancer associated-mutant ubiquitin ligases. Our lab combines genetic and proteomic-based approaches to identify and elucidate novel substrate-ligase pairings and their biological significance in sustaining the proliferation of cancer B-cells.
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82 (ii) Development of high-throughput assays to identify small molecules targeting ubiquitin ligase-substrate interactions.
f9 With this research area, we aim to establish assays to serve as a screening platform for targeting specific ligase-substrate interactions. Our long-term goal is to identify candidate molecules to test them in models of leukemia and lymphoma.
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1d Lab Personnel:
16 Sehbanul Islam
14 Mukul Mishra
13 Jiadong Tao
15 Monika Mittal
1b Karthik Prabakaran
14 Aqsa Yashfeen
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Description of Research Expertise
28 Current Research201 My laboratory studies the mechanisms by which the ubiquitin-proteasome system (UPS) controls cell proliferation and how alterations in these processes contribute to tumor initiation and maintenance. Misregulation of protein degradation pathways is often observed in cancer cells. Integrating the study of cellular signals with the molecular mechanisms by which ubiquitin ligases target substrates will advance our knowledge of cancer biology and will provide novel avenues for development of therapeutics.
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11e Areas of interest within the laboratory include, but are not limited to: (i) Signaling Pathways (such as those related to the cell division cycle, DNA damage response, circadian clock, and NFkB signaling) and (ii) Identification of small molecules to target ubiquitin ligases.
8
19 Busino Lab
20f Hematological malignancies are tumors that affect blood, bone marrow and lymph nodes. Taken together, hematological malignancies account for approximately 10% of new cancer diagnoses in the United States. Drugs that target the UPS, such as thalidomide and bortezomib, improve survival, underlining the effectiveness of targeting the UPS, but resistance to these therapies eventually develops. Therefore, the identification of novel UPS enzymes that could serve as targets is crucial for the development of therapeutics.
8
40 My laboratory focuses on two main research areas:
5d (i) Functional discoveries in the area of ubiquitin system and hematologic diseases.
13f This research area aims to characterize the molecular functions of cancer associated-mutant ubiquitin ligases. Our lab combines genetic and proteomic-based approaches to identify and elucidate novel substrate-ligase pairings and their biological significance in sustaining the proliferation of cancer B-cells.
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82 (ii) Development of high-throughput assays to identify small molecules targeting ubiquitin ligase-substrate interactions.
f9 With this research area, we aim to establish assays to serve as a screening platform for targeting specific ligase-substrate interactions. Our long-term goal is to identify candidate molecules to test them in models of leukemia and lymphoma.
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1d Lab Personnel:
16 Sehbanul Islam
14 Mukul Mishra
13 Jiadong Tao
15 Monika Mittal
1b Karthik Prabakaran
14 Aqsa Yashfeen
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ec Busino L, Chiesa M, Draetta GF, Donzelli M: Cdc25A phosphatase: combinatorial phosphorylation, ubiquitylation and proteolysis. Oncogene 23(11): 2050-6, March 2004.
10d Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta GF: Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell Cycle 3(4): 469-71, April 2004.
133 Busino L, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, Draetta GF, Pagano M: SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins. Science 316(5826): 900-4, May 2007.
87 Busino L, Millman SE, Kyratsous C, Scotto L, Basrur V, Hoffmann A, O’Connor O, Elenitoba- b9 Johnson K, Pagano M: SCFFbxw7-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature Cell Biology 14(4): 375-85, March 2012.
108 Xing W, Busino L, Hinds TR, Marionni ST, Saifee NH, Bush MF, Pagano M, Zheng N: SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature 496(7443): 64-8, April 2013.
147 Choi J, Lee K, Ingvarsdottir K, Bonasio R, Saraf A, Florens L, Washburn MP, Tadros S, Green MR, Busino L: Loss of KLHL6 promotes DLBCL growth and survival via stabilization of the mRNA decay factor Roquin2. Nature Cell Biology 20(5): 586-596, April 2018.
ed Choi J, Saraf A, Florens L, Washburn MP, Busino L: PTPN14 regulates Roquin2 stability by tyrosine dephosphorylation. Cell Cycle 17(18): 2243–2255, September 2018.
157 Zhou N, Uzquiza AG, Zheng XY, Vogl D, Garfall AL, Bernabei L, Saraf A, Florens L, Washburn MP, Illendula A, Bushweller JH, Busino L: RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation. Leukemia 33(8): 2006-2021, August 2019.
1e1 Guillamot M, Ouazia D, Dolgalev I, Kourtis N, Dai Y, Corrigan K, Yeung S, Zea-Redondo L, Saraf A, Florens L, Washburn MP, Tikhonova AN, Gong Y, Tsirigos A, Park C, Barbieri C, Khanna K, Busino L*, Aifantis I* (*co-last and co-corresponding authors): The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MyD88 degradation. Nature Immunology 20(9): 1196-1207, September 2019.
122 Saffie R, Rolland DCM, Onder O, Basrur V, Elenitoba-Johnson KSJ, Capell BC, Busino L: FBXW7 triggers degradation of KMT2D to favor growth of mature B-type malignant cells. Cancer Research 80(12): 2498-2511, June 2020.
1af Simoneschi D, Rona G, Zhou N, Jeong YT, Jiang S, Milletti G, Arbini AA, O'Sullivan A, Wang AA, Nithikasem S, Keegan S, Siu Y, Cianfanelli V, Maiani E, Nazio F, Cecconi F, Boccalatte F, Fenyö D, Jones DR, Busino L*, Pagano M* (*co-last and co-corresponding authors): CRL4-AMBRA1 is a master regulator of D-type cyclins. Nature 592(7856): 789-793, April 2021.
173 Zhou N, Choi J, Grothusen G, Kim BJ, Ren D, Cao Z, Liu Y, Li Q, Inamdar A, Beer T, Tang HY, Perkey E, Maillard I, Bonasio R, Shi J, Ruella M, Wan L, Busino L.: DLBCL associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance. Blood 142(11): 973-988, Sep 14 2023.
17b Grothusen GP, Chang R, Cao Z, Zhou N, Mittal M, Datta A, Wulfridge P, Beer T, Wang B, Zheng N, Tang HY, Sarma K, Greenberg RA, Shi J, Busino L.: DCAF15 control of cohesin dynamics sustains acute myeloid leukemia. Nat Commun 15(1): 5604, July 3 2024 Notes: doi: 10.1038/s41467-024-49882-x. Free PMC article.
15b Islam S, Gour J, Beer T, Tang HY, Cassel J, Salvino JM, Busino L.: A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins. ACS Chem Biol 16;19(2): 233-242, Feb 16 2024 Notes: doi: 10.1021/acschembio.3c00570. Epub 2024 Jan 25.
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Selected Publications
12a Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF: Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 426(6962): 87-91, November 2003.ec Busino L, Chiesa M, Draetta GF, Donzelli M: Cdc25A phosphatase: combinatorial phosphorylation, ubiquitylation and proteolysis. Oncogene 23(11): 2050-6, March 2004.
10d Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta GF: Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell Cycle 3(4): 469-71, April 2004.
133 Busino L, Bassermann F, Maiolica A, Lee C, Nolan PM, Godinho SI, Draetta GF, Pagano M: SCFFbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins. Science 316(5826): 900-4, May 2007.
87 Busino L, Millman SE, Kyratsous C, Scotto L, Basrur V, Hoffmann A, O’Connor O, Elenitoba- b9 Johnson K, Pagano M: SCFFbxw7-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature Cell Biology 14(4): 375-85, March 2012.
108 Xing W, Busino L, Hinds TR, Marionni ST, Saifee NH, Bush MF, Pagano M, Zheng N: SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket. Nature 496(7443): 64-8, April 2013.
147 Choi J, Lee K, Ingvarsdottir K, Bonasio R, Saraf A, Florens L, Washburn MP, Tadros S, Green MR, Busino L: Loss of KLHL6 promotes DLBCL growth and survival via stabilization of the mRNA decay factor Roquin2. Nature Cell Biology 20(5): 586-596, April 2018.
ed Choi J, Saraf A, Florens L, Washburn MP, Busino L: PTPN14 regulates Roquin2 stability by tyrosine dephosphorylation. Cell Cycle 17(18): 2243–2255, September 2018.
157 Zhou N, Uzquiza AG, Zheng XY, Vogl D, Garfall AL, Bernabei L, Saraf A, Florens L, Washburn MP, Illendula A, Bushweller JH, Busino L: RUNX proteins desensitize multiple myeloma to lenalidomide via protecting IKZFs from degradation. Leukemia 33(8): 2006-2021, August 2019.
1e1 Guillamot M, Ouazia D, Dolgalev I, Kourtis N, Dai Y, Corrigan K, Yeung S, Zea-Redondo L, Saraf A, Florens L, Washburn MP, Tikhonova AN, Gong Y, Tsirigos A, Park C, Barbieri C, Khanna K, Busino L*, Aifantis I* (*co-last and co-corresponding authors): The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MyD88 degradation. Nature Immunology 20(9): 1196-1207, September 2019.
122 Saffie R, Rolland DCM, Onder O, Basrur V, Elenitoba-Johnson KSJ, Capell BC, Busino L: FBXW7 triggers degradation of KMT2D to favor growth of mature B-type malignant cells. Cancer Research 80(12): 2498-2511, June 2020.
1af Simoneschi D, Rona G, Zhou N, Jeong YT, Jiang S, Milletti G, Arbini AA, O'Sullivan A, Wang AA, Nithikasem S, Keegan S, Siu Y, Cianfanelli V, Maiani E, Nazio F, Cecconi F, Boccalatte F, Fenyö D, Jones DR, Busino L*, Pagano M* (*co-last and co-corresponding authors): CRL4-AMBRA1 is a master regulator of D-type cyclins. Nature 592(7856): 789-793, April 2021.
173 Zhou N, Choi J, Grothusen G, Kim BJ, Ren D, Cao Z, Liu Y, Li Q, Inamdar A, Beer T, Tang HY, Perkey E, Maillard I, Bonasio R, Shi J, Ruella M, Wan L, Busino L.: DLBCL associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemoresistance. Blood 142(11): 973-988, Sep 14 2023.
17b Grothusen GP, Chang R, Cao Z, Zhou N, Mittal M, Datta A, Wulfridge P, Beer T, Wang B, Zheng N, Tang HY, Sarma K, Greenberg RA, Shi J, Busino L.: DCAF15 control of cohesin dynamics sustains acute myeloid leukemia. Nat Commun 15(1): 5604, July 3 2024 Notes: doi: 10.1038/s41467-024-49882-x. Free PMC article.
15b Islam S, Gour J, Beer T, Tang HY, Cassel J, Salvino JM, Busino L.: A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins. ACS Chem Biol 16;19(2): 233-242, Feb 16 2024 Notes: doi: 10.1021/acschembio.3c00570. Epub 2024 Jan 25.
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