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Dhifaf Sarhan

Assistant professor

Department and organisational affiliation:

About me

Recently recruited as Assistant Professor in Tumor immunology/Immunotherapy to the Department of Microbiology, Tumor and Cell Biology (MTC). I received my Ph.D. degree from the Department of Oncology-Pathology, Karolinska Institutet in 2014 followed by a postdoctoral training at the University of Minnesota. In 2018, I joined MTC. My research interest focuses on studying the consequences of the tumor microenvironment (TME) on shaping the immune effector cell function and memory aiming to remodel the TME to improved cancer immunotherapies.

Research description

Project I: Antibody targeting of suppressive myeloid cells for cancer immunotherapy

The goal for this project is to identify specific targets for tumor-associated macrophages and myeloid-derived suppresor cells to reprogram their suppressive nature and later develop target antibodies to relieve the anti-tumor activity of Natural Killer (NK) cells and T cells. Currently we are studying the Scavenger receptors and g-coupled protein receptor as therapeutic targets in pancreas and lung cancer. 

 

Project II: Study the mechanisms of immune exclusion in pancreatic tumors highly infiltrated by myeloid cells

In this project, we study the myeloid cell-dependent inhibition mechanisms of NK and T cell infiltration into cold and immune excluded pancreas tumors. Patient tumor and blood specimens are provided by national and international collaborators. Further, we are extensively examining the receptor signal integration in suppressive myeloid cells and the impact of gender dimorphism on the TME in pancreatic cancer 

 

Project III: Adaptive NK cell immunological memory in cancer

For decades NK cells were believed to lack immunological memory, however recent groundbreaking research by us and others revealed the opposite. We discovered novel mechanisms used by adaptive NK cells to resist the suppressive tumor environment. In this project we focus on investigating the molecular mechanisms behind NK cell memory and the crosstalk with antigen presenting cells like dendritic cells and B cells in cancer. 

 

 

Lab members:

Dhifaf Sarhan, Assistant professor

Fei He, PhD student

Catarina Pelicano, Erasmus internship programme

Martin Borgmann, Erasmus internship programme

 

Alumni:

Suborna Mastafa, Bachelor thesis project, 2019, Karolinska Institutet

Caroline Driescher, Master thesis project, 2018, Karolinska Institutet

 

 

Academic honours, awards and prizes

Jonas Söderquist's scholarship

Pancreatic cancer fellow, Swedish Cancer Society

Postdoctoral fellowship, Karolinska Institutet and University of Minnesota, Minneapolis, Minnesota USA

Award for research-project, ImmunoTools

Scholarship, Swedish Order of Freemasons

 

Funding

Current

Jonas Söderquist foundation

Swedish Cancer Society

KI Stiftelser och Fonder

Stiftelsen Sigurd and Elsa Goljes Minne

Radiumhemmet

The Sjöberg foundation

Past

Postdoctoral fellowship Karolinska Institutet, University of Minnesota

Novo, NovoSeeds

Robert Lundbergs minnesstiftelse

 

Publication

Original articles

1. Sarhan D, Brandt L, Felices M, Guldevall K, Lenvik T, Hinderlie P, Curtsinger J, Warlick E, Spellman SR, Blazar BR, Weisdorf DJ, Cooley S, Vallera DA, Önfelt B, Miller JS. 161533 TriKE stimulates NK-cell function to overcome myeloid-derived suppressor cells in MDS. Blood Adv. 2018

2. Sarhan D, Hippen KL, Lemire A, Hying S, Luo X, Lenvik T, Curtsinger J, Davis Z, Zhang B, Cooley S, Cichocki F, Blazar BR, Miller JS. Adaptive NK Cells Resist Regulatory T-cell Suppression Driven by IL37. Cancer Immunol Res. 2018

3. de Witte MA, Sarhan D, Davis Z, Felices M, Vallera DA, Hinderlie P, Curtsinger J, Cooley S, Wagner J, Kuball J, Miller JS. Early Reconstitution of NK and γδ T Cells and Its Implication for the Design of Post-Transplant Immunotherapy. Biol Blood Marrow Transplant, 2018. 

4. Bachanova V, Sarhan D, DeFor TE, Cooley S, Panoskaltsis-Mortari A, Blazar BR, Curtsinger JM, Burns L, Weisdorf DJ, Miller JS. Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer immunology,immunotherapy : CII 2018 67;3 483-494

5. Sarhan D*, Leijonhufvud C*, Murray S, Witt K, Seitz C, Wallerius M, Xie HJ, Ullen A, Harmenberg U, Lidbrink E, Rolny C, Andersson J, Lundqvist A. Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer. ONCOIMMUNOLOGY 2017 6;8 e1338238-

6. Cichocki F, Valamehr B, Bjordahl R, Zhang B, Rezner B, Rogers P, Gaidarova S, Moreno S, Tuininga K, Dougherty P, McCullar V, Howard P, Sarhan D, Taras E, Schlums H, Abbot S, Shoemaker D, Bryceson YT, Blazar BR, Wolchko S, Cooley S, Miller JS. GSK3 Inhibition Drives Maturation of NK Cells and Enhances Their Antitumor Activity. Cancer research 2017 77;20 5664-5675

7. Lövgren T, Sarhan D, Truxová I, Choudhary B, Maas R, Melief J, Nyström M, Edbäck U, Vermeij R, Scurti G, Nishimura M, Masucci G, Karlsson-Parra A, Lundqvist A, Adamson L, Kiessling R. Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon-γ and multiple toll-like receptor agonists. Cancer immunology, immunotherapy: CII 2017 66;10 1333-1344

8. Luu TT, Ganesan S, Wagner AK, Sarhan D, Meinke S, Garbi N, Hämmerling G, Alici E, Kärre K, Chambers BJ, Höglund P, Kadri N. Independent control of natural killer cell responsiveness and homeostasis at steady-state by CD11c+ dendritic cells. Scientific reports 2016 6; 37996-

9. Sarhan D, Cichocki F, Zhang B, Yingst A, Spellman SR, Cooley S, Verneris MR, Blazar BR, Miller JS. Adaptive NK Cells with Low TIGIT Expression Are Inherently Resistant to Myeloid-Derived Suppressor Cells. CANCER RESEARCH 2016 76;19 5696-5706

10. Sarhan D, Palma M, Mao Y, Adamson L, Kiessling R, Mellstedt H, Österborg A, Lundqvist A. Dendritic cell regulation of NK-cell responses involves lymphotoxin-α, IL-12, and TGF-β. European journal of immunology 2015 45;6 1783-93

11. Mao Y*, Sarhan D*, Steven A, Seliger B, Kiessling R,  Lundqvist A. Inhibition of tumor-derived prostaglandin-e2 blocks the induction of myeloid-derived suppressor cells and recovers natural killer cell activity. Clinical cancer research: an official journal of the American Association for Cancer Research 2014 20;15 4096-106

12. Sarhan D, Wennerberg E,  D'Arcy P,  Gurajada D,  Linder S,  Lundqvist A. A novel inhibitor of proteasome deubiquitinating activity renders tumor cells sensitive to TRAIL-mediated apoptosis by natural killer cells and T cells. Cancer immunology, immunotherapy: CII 2013 62;8 1359-68

13. Wennerberg E, Sarhan D, Carlsten M, Kaminskyy VO,  D'Arcy P,  Zhivotovsky B,  Childs R,  Lundqvist A. Doxorubicin sensitizes human tumor cells to NK cell- and T-cell-mediated killing by augmented TRAIL receptor signaling. International journal of cancer 2013 133;7 1643-52

14. Sarhan D, D'Arcy P, Wennerberg E,  Lidén M,  Hu J,  Winqvist O,  Rolny C,  Lundqvist A. Activated monocytes augment TRAIL-mediated cytotoxicity by human NK cells through release of IFN-γ. European journal of immunology 2013

15. Okita R, Mougiakakos D, Ando T,  Mao YM,  Sarhan D,  Wennerberg E,  Seliger B,  Lundqvist A,  Mimura K,  Kiessling R. HER2/HER3 Signaling Regulates NK Cell-Mediated Cytotoxicity via MHC Class I Chain-Related Molecule A and B Expression in Human Breast Cancer Cell Lines. JOURNAL OF IMMUNOLOGY 2012 188;5 2136-45

Reviews

1. Dahlberg CI, Sarhan D,  Chrobok M,  Duru AD,  Alici E. Natural Killer Cell-Based Therapies Targeting Cancer: Possible Strategies to Gain and Sustain Anti-Tumor Activity. Frontiers in immunology 2015 6; 605-

2. Sarhan D, D'Arcy P, Lundqvist A. Regulation of TRAIL-receptor expression by the ubiquitin-proteasome system. International journal of molecular sciences 2014 15;10 18557-73

3. Kiessling R, Okita R,  Mougiakakos D,  Mao YM,  Sarhan D,  Wennerberg E,  Seliger B,  Lundqvist A,  Mimura K,  Kono K. Opposing consequences of signaling through EGF family members Escape from CTLs could be a bait for NK cells. ONCOIMMUNOLOGY 2012 1;7 1200-1201

Book chapters

- Sarhan D,  Miller JS. Cell and Gene Therapies, Natural Killer Cells-What have we learned?, Springer Nature, 2019

- Sarhan D,  Miller JS. Immune checkpoint blockade, Assessing Canonical and Adaptive Natural Killer Cell Function in Suppression Assays In Vitro. Methods in molecular biology (Clifton, N.J.) 2019 1913; 153-166

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