Keyoumars Soltani
· Emeritus FacultyUniversity of Chicago · Dermatology and Molecular Sciences
Active 1972–2023
About
Keyoumars Soltani is a Professor at the University of Chicago in the Department of Medicine-Dermatology. His research focuses on dermatopathology, skin diseases, and the molecular mechanisms underlying skin carcinogenesis and repair. His work includes studying the regulation of DNA damage repair, the role of autophagy in inflammation and tumorigenesis, and the effects of ultraviolet radiation on skin cells. He has contributed to understanding the pathogenesis of various dermatological conditions, including pemphigoid, psoriasis, and skin cancers, through both clinical and molecular research. Throughout his career, Professor Soltani has published extensively, with research spanning topics such as immunohistochemistry for diagnosis, the impact of immunosuppressive agents on skin cancer risk, and the molecular pathways involved in skin disease progression. His work often involves exploring the genetic and cellular responses to environmental factors like UV radiation and therapeutic agents, aiming to improve diagnostic accuracy and develop targeted treatments for skin disorders.
Research topics
- Computer Science
- Cancer research
- Data Mining
- Genetics
- Biology
- Pathology
- Chemistry
- Computational biology
- Immunology
- Molecular biology
- Medicine
- Dermatology
- Database
Selected publications
2023
- Computer Science
- Data Mining
- Computational biology
<p>PDF file - 256K</p>
2023-04-03
preprintOpen access<div>Abstract<p>Skin cancer is the most common malignancy in organ transplant recipients, causing serious morbidity and mortality. Preventing and treating skin cancer in these individuals has been extraordinarily challenging. Following organ transplantation, cyclosporin A (CsA) has been used as an effective immunosuppressive to prevent rejection. Therefore immunosuppression has been widely assumed to be the major cause for increased skin carcinogenesis. However, the mechanism of skin carcinogenesis in organ transplant recipients has not been understood to date; specifically, it remains unknown whether these cancers are immunosuppression dependent or independent. Here, using both immunocompromised nude mice which are defective in mature T lymphocytes as an <i>in vivo</i> model and human keratinocytes as an <i>in vitro</i> model, we showed that CsA impairs genomic integrity in the response of keratinocytes to ultra violet B (UVB). Following UVB radiation, CsA inhibited UVB-induced DNA damage repair by suppressing the transcription of the DNA repair factor xeroderma pigmentosum C (XPC). In addition, CsA compromised the UVB-induced checkpoint function by upregulating the molecular chaperone protein cyclophilin A (CypA). XPC mRNA levels were lower, whereas CypA mRNA and protein levels were higher in human skin cancers than in normal skin. CsA-induced phosphoinositide 3-kinase(PI3K)/AKT activation was required for both XPC suppression and CypA upregulation. Blocking UVB damage or inhibiting the PI3K/AKT pathway prevented CsA-sensitized skin tumorigenesis. Our findings identified deregulation of XPC and CypA as key targets of CsA, and UVB damage and PI3K/AKT activation as two principal drivers for CsA-sensitized skin tumorigenesis, further supporting an immunosuppression-independent mechanism of CsA action on skin tumorigenesis. <i>Cancer Prev Res; 5(9); 1155–62. ©2012 AACR</i>.</p></div>
2023-04-03
preprintOpen access<p>PDF file - 332K, Supplemental materials and methods 2. Fig. s1. CsA down-regulates PTEN levels in non-tumor skin and tumors from UVB-irradiated mice and skin from sham- irradiated mice by immunohistochemical analysis. 3. Fig. s2. Alteration of CypA expression by CsA and in skin cancers. 4. Fig. s3. CypA had no effect on XPC levels, AKT activation, or UVB-induced DNA damage repair. 5. Fig. s4. The Effect of CsA on ATF3 levels and the role of Calcineurin B1 (CnB1)</p>
2023
- Computer Science
- Computer Science
- Cancer research
<p>PDF file - 256K</p>
Data from PTEN Positively Regulates UVB-Induced DNA Damage Repair
2023-03-30
preprintOpen access<div>Abstract<p>Nonmelanoma skin cancer is the most common cancer in the United States, where DNA-damaging ultraviolet B (UVB) radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared with skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCCs, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin through its ability to positively regulate XPC-dependent GG-NER following DNA damage. <i>Cancer Res; 71(15); 5287–95. ©2011 AACR</i>.</p></div>
Data from PTEN Positively Regulates UVB-Induced DNA Damage Repair
2023-03-30
preprintOpen access<div>Abstract<p>Nonmelanoma skin cancer is the most common cancer in the United States, where DNA-damaging ultraviolet B (UVB) radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared with skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCCs, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin through its ability to positively regulate XPC-dependent GG-NER following DNA damage. <i>Cancer Res; 71(15); 5287–95. ©2011 AACR</i>.</p></div>
2023-04-03
preprintOpen access<div>Abstract<p>Skin cancer is the most common malignancy in organ transplant recipients, causing serious morbidity and mortality. Preventing and treating skin cancer in these individuals has been extraordinarily challenging. Following organ transplantation, cyclosporin A (CsA) has been used as an effective immunosuppressive to prevent rejection. Therefore immunosuppression has been widely assumed to be the major cause for increased skin carcinogenesis. However, the mechanism of skin carcinogenesis in organ transplant recipients has not been understood to date; specifically, it remains unknown whether these cancers are immunosuppression dependent or independent. Here, using both immunocompromised nude mice which are defective in mature T lymphocytes as an <i>in vivo</i> model and human keratinocytes as an <i>in vitro</i> model, we showed that CsA impairs genomic integrity in the response of keratinocytes to ultra violet B (UVB). Following UVB radiation, CsA inhibited UVB-induced DNA damage repair by suppressing the transcription of the DNA repair factor xeroderma pigmentosum C (XPC). In addition, CsA compromised the UVB-induced checkpoint function by upregulating the molecular chaperone protein cyclophilin A (CypA). XPC mRNA levels were lower, whereas CypA mRNA and protein levels were higher in human skin cancers than in normal skin. CsA-induced phosphoinositide 3-kinase(PI3K)/AKT activation was required for both XPC suppression and CypA upregulation. Blocking UVB damage or inhibiting the PI3K/AKT pathway prevented CsA-sensitized skin tumorigenesis. Our findings identified deregulation of XPC and CypA as key targets of CsA, and UVB damage and PI3K/AKT activation as two principal drivers for CsA-sensitized skin tumorigenesis, further supporting an immunosuppression-independent mechanism of CsA action on skin tumorigenesis. <i>Cancer Prev Res; 5(9); 1155–62. ©2012 AACR</i>.</p></div>
2023-04-03
preprintOpen access<p>PDF file - 332K, Supplemental materials and methods 2. Fig. s1. CsA down-regulates PTEN levels in non-tumor skin and tumors from UVB-irradiated mice and skin from sham- irradiated mice by immunohistochemical analysis. 3. Fig. s2. Alteration of CypA expression by CsA and in skin cancers. 4. Fig. s3. CypA had no effect on XPC levels, AKT activation, or UVB-induced DNA damage repair. 5. Fig. s4. The Effect of CsA on ATF3 levels and the role of Calcineurin B1 (CnB1)</p>
American Journal of Dermatopathology · 2022 · 29 citations
- Medicine
- Pathology
- Dermatology
ABSTRACT: Immune checkpoint inhibitors are increasingly being used in the treatment of various solid organ and hematologic malignancies. Dermatologic toxicities associated with programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) therapy have been widely reported in the literature. It is important for clinicians to be aware of these toxicities to ensure prompt recognition and treatment. Herein, we present the clinical, histopathologic, and immunofluorescence findings of 3 patients diagnosed with lichen planus pemphigoides (LPP) after treatment with anti-PD-1 inhibitors. We also reviewed the literature and summarize 7 previously reported cases of LPP associated with anti-PD-1 and anti-PD-L1 inhibitors. LPP was diagnosed at a median time of 24.4 weeks (range: 4-78 weeks) after initiation of immunotherapy. Clinical findings included papules, plaques, erosions, vesicles, and bullae on the trunk and extremities. Oral involvement was present in half the cases. Histopathologic features of immunotherapy-induced LPP included lichenoid or vacuolar interface dermatitis, the presence of eosinophils, and subepidermal bullae. Direct immunofluorescence demonstrated linear deposition of immunoglobulin G (IgG) or C3. Indirect immunofluorescence demonstrated linear IgG along basement membrane zone on monkey esophagus in 2 cases and linear IgG on the epidermal side of salt split skin in 3 cases. Serum anti-BP180 was elevated in all cases in which enzyme-linked immunosorbent assay was performed.
Cancer Research · 2018-07-01
articleAbstract UV radiation is a major risk factor for skin cancer, the most common cancer in the United States. UV exposure leads to DNA damage by formation of dimers between adjacent pyrimidine bases. The nucleotide excision repair (NER) process is responsible for removal of UV-induced DNA damage. When the damage is left unrepaired due to inefficient NER in disorders like xeroderma pigmentosum, it leads to skin tumorigenesis. Although the main players of the NER pathway have been characterized, the molecular regulation of the pathway is less understood. Understanding the regulation, particularly post-translational regulation, of the NER pathway has the potential to yield modulators of NER efficiency to prevent skin cancer. We found that chronic UV irradiation led to down-regulation of ubiquitin specific peptidase 11 (USP11) in mouse skin tissue. We also found that USP11 is decreased in skin tumors in mice and humans. Moreover, high-throughput proteomics analysis had predicted that USP11 may interact with NER factor XPC. Hence, we undertook this study to determine the role of USP11 in NER and cellular response to UV. We found that USP11 promoted the NER pathway by regulating XPC activity. USP11 promoted XPC deubiquitination and retention at the DNA damage sites. We also found that USP11 interaction with ubiquitinated XPC was enhanced post-UV irradiation, and that USP11 was recruited to the chromatin post-UV damage. Further, squamous cell carcinoma cells showed reduced survival with inhibition of USP11 after UV exposure. Our findings indicate that USP11 plays an important role in maintaining NER capacity, and suggest that USP11 acts as a tumor suppressor via its role in DNA repair. Citation Format: Palak Shah, Lei Qiang, Seungwon Yang, Keyoumars Soltani, Yu-Ying He. USP11 regulates UV-induced DNA damage repair and cell survival associated with skin cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4155.
Frequent coauthors
- 26 shared
Christopher R. Shea
- 22 shared
Allan L. Lorincz
University of Chicago
- 18 shared
N Reply
New York Proton Center
- 15 shared
Iris K. Aronson
Zionsville Community High School
- 15 shared
Yu‐Ying He
University of Chicago
- 15 shared
Weinong Han
- 13 shared
Cheuk W. Yung
University of Chicago
- 13 shared
Joel E. Bernstein
Education
- 2000
M.D., Medicine
University of Chicago
- 1996
B.S., Biology
University of California, San Diego
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