Dr Heba Ismail

MSc, PhD, FHEA

School of Medicine and Population Health

Lecturer in Chronic Disease Biology

H.Ismail@sheffield.ac.uk
+44 114 222 2390

Firth Court

Full contact details

Dr Heba Ismail
School of Medicine and Population Health
Firth Court
Western Bank
Sheffield
S10 2TN

Profile

I am currently a research group leader and lecturer in the Molecular Medicine division, Faculty of Health, at the University of Sheffield.

My academic journey led me to obtain a PhD in Biochemistry and Molecular Biology from University College London (UCL), which I completed in 2009. I then joined Professor Jeremy Saklatvala’s laboratory at the Kennedy Institute of Rheumatology (Imperial College London) as a postdoctoral research fellow, where I developed a keen interest in the molecular mechanisms underlying osteoarthritis.

In 2011, I moved to the University of Oxford as a senior postdoctoral fellow within the Osteoarthritis Centre of Excellence. My research there focused on the cellular events triggered by mechanical tissue injury, leading to the identification of key upstream mechanisms driving tissue damage in osteoarthritis.

In 2018, I was awarded a Career Development Fellowship (CDF) by Versus Arthritis to investigate the ubiquitination machinery and enzymes mediating connective tissue injury, which are critical for the development of disease-modifying therapies for osteoarthritis and other musculoskeletal disorders. This fellowship enabled me to relocate to the University of Sheffield where I established my research group.

Research interests

Research in my lab uncovers the cellular mechanisms driving chronic inflammation and tissue damage in musculoskeletal diseases, with a particular focus on osteoarthritis. We aim to redefine therapeutic strategies for osteoarthritis by disrupting the vicious cycle of mechanical injury and inflammation.

Our primary focus is on the ubiquitination machinery that mediates inflammatory responses triggered by mechanical stress. By targeting these pathways, we seek to develop disease-modifying therapies for osteoarthritis and related musculoskeletal conditions. Beyond osteoarthritis, our research also explores how the ubiquitin system contributes to mechanoflammation in the contexts of ageing, multimorbidity, and cancer.

To achieve these goals, we employ a range of advanced in vivo and ex vivo models, including murine and zebrafish systems, as well as human and porcine tissues. Our toolkit includes cutting-edge technologies such as advanced transgenesis, in vivo live imaging with light-sheet and confocal microscopy, functional genomics using CRISPR/Cas9-based loss-of-function and gain-of-function screens, mass spectrometry, and diverse biochemical approaches. These methodologies allow us to dissect the function and regulation of the ubiquitin system in both in vivo and in vitro settings.

Publications

Show: Featured publications All publications

Featured publications

Journal articles

Khalil MI, Ismail HM, Panasyuk G, Bdzhola A, Filonenko V, Gout I & Pardo OE (2023) Asymmetric dimethylation of ribosomal S6 kinase 2 regulates its cellular localisation and pro-survival function. International Journal of Molecular Sciences, 24(10). View this article in WRRO
Oliviero S, Millard E, Chen Z, Rayson A, Roberts BC, Ismail HMS, Bellantuono I & Dall’Ara E (2023) Accuracy of in vivo microCT imaging in assessing the microstructural properties of the mouse tibia subchondral bone. Frontiers in Endocrinology, 13. View this article in WRRO
Zhu L, Kamalathevan P, Koneva LA, Zarebska JM, Chanalaris A, Ismail H, Wiberg A, Ng M, Muhammad H, Walsby-Tickle J , McCullagh JSO et al (2022) Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis. Science Translational Medicine, 14(676).
Kaokhum N, Pinto-Fernández A, Wilkinson M, Kessler BM & Ismail HM (2022) The mechano-ubiquitinome of articular cartilage: differential ubiquitination and activation of a group of ER-associated DUBs and ER stress regulators. Molecular & Cellular Proteomics.
Southan J, McHugh E, Walker H & Ismail H (2020) Metabolic signature of articular cartilage following mechanical injury: An integrated transcriptomics and metabolomics analysis. Frontiers in Molecular Biosciences, 7. View this article in WRRO
Ismail HM, Didangelos A, Vincent TL & Saklatvala J (2017) Rapid Activation of Transforming Growth Factor β-Activated Kinase 1 in Chondrocytes by Phosphorylation and K63-Linked Polyubiquitination Upon Injury to Animal Articular Cartilage. Arthritis & Rheumatology, 69(3), 565-575.
Ismail HM, Miotla-Zarebska J, Troeberg L, Tang X, Stott B, Yamamoto K, Nagase H, Fosang AJ, Vincent TL & Saklatvala J (2016) Brief Report: JNK‐2 Controls Aggrecan Degradation in Murine Articular Cartilage and the Development of Experimental Osteoarthritis. Arthritis & Rheumatology, 68(5), 1165-1171.
Driscoll C, Chanalaris A, Knights C, Ismail H, Sacitharan PK, Gentry C, Bevan S & Vincent TL (2016) Nociceptive Sensitizers Are Regulated in Damaged Joint Tissues, Including Articular Cartilage, When Osteoarthritic Mice Display Pain Behavior. Arthritis & Rheumatology, 68(4), 857-867.
Ismail HM, Yamamoto K, Vincent TL, Nagase H, Troeberg L & Saklatvala J (2015) Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation by Human Chondrocytes. Arthritis & Rheumatology, 67(7), 1826-1836.
Ismail HMS, Hurd PJ, Khalil MIM, Kouzarides T, Bannister A & Gout I (2014) S6 Kinase 2 Is Bound to Chromatin-Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo. Journal of Cellular Biochemistry, 115(6), 1048-1062.
Ismail HMS, Myronova O, Tsuchiya Y, Niewiarowski A, Tsaneva I & Gout I (2013) Identification of the general transcription factor Yin Yang 1 as a novel and specific binding partner for S6 Kinase 2. Cellular Signalling, 25(5), 1054-1063.
Watt FE, Ismail HM, Didangelos A, Peirce M, Vincent TL, Wait R & Saklatvala J (2013) Src and fibroblast growth factor 2 independently regulate signaling and gene expression induced by experimental injury to intact articular cartilage. Arthritis & Rheumatism, 65(2), 397-407.
Hurd PJ, Bannister AJ, Halls K, Dawson MA, Vermeulen M, Olsen JV, Ismail H, Somers J, Mann M, Owen-Hughes T , Gout I et al (2009) Phosphorylation of Histone H3 Thr-45 Is Linked to Apoptosis. Journal of Biological Chemistry, 284(24), 16575-16583.

All publications

Journal articles

Khalil MI, Ismail HM, Panasyuk G, Bdzhola A, Filonenko V, Gout I & Pardo OE (2023) Asymmetric dimethylation of ribosomal S6 kinase 2 regulates its cellular localisation and pro-survival function. International Journal of Molecular Sciences, 24(10). View this article in WRRO
Oliviero S, Millard E, Chen Z, Rayson A, Roberts BC, Ismail HMS, Bellantuono I & Dall’Ara E (2023) Accuracy of in vivo microCT imaging in assessing the microstructural properties of the mouse tibia subchondral bone. Frontiers in Endocrinology, 13. View this article in WRRO
Zhu L, Kamalathevan P, Koneva LA, Zarebska JM, Chanalaris A, Ismail H, Wiberg A, Ng M, Muhammad H, Walsby-Tickle J , McCullagh JSO et al (2022) Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis. Science Translational Medicine, 14(676).
Kaokhum N, Pinto-Fernández A, Wilkinson M, Kessler BM & Ismail HM (2022) The mechano-ubiquitinome of articular cartilage: differential ubiquitination and activation of a group of ER-associated DUBs and ER stress regulators. Molecular & Cellular Proteomics.
Southan J, McHugh E, Walker H & Ismail H (2020) Metabolic signature of articular cartilage following mechanical injury: An integrated transcriptomics and metabolomics analysis. Frontiers in Molecular Biosciences, 7. View this article in WRRO
Ismail HM, Didangelos A, Vincent TL & Saklatvala J (2017) Rapid Activation of Transforming Growth Factor β-Activated Kinase 1 in Chondrocytes by Phosphorylation and K63-Linked Polyubiquitination Upon Injury to Animal Articular Cartilage. Arthritis & Rheumatology, 69(3), 565-575.
Ismail HM, Miotla-Zarebska J, Troeberg L, Tang X, Stott B, Yamamoto K, Nagase H, Fosang AJ, Vincent TL & Saklatvala J (2016) Brief Report: JNK‐2 Controls Aggrecan Degradation in Murine Articular Cartilage and the Development of Experimental Osteoarthritis. Arthritis & Rheumatology, 68(5), 1165-1171.
Driscoll C, Chanalaris A, Knights C, Ismail H, Sacitharan PK, Gentry C, Bevan S & Vincent TL (2016) Nociceptive Sensitizers Are Regulated in Damaged Joint Tissues, Including Articular Cartilage, When Osteoarthritic Mice Display Pain Behavior. Arthritis & Rheumatology, 68(4), 857-867.
Ismail HM, Yamamoto K, Vincent TL, Nagase H, Troeberg L & Saklatvala J (2015) Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation by Human Chondrocytes. Arthritis & Rheumatology, 67(7), 1826-1836.
El-Halawany MS, Ismail HM, Zeeneldin AA, Elfiky A, Tantawy M, Kobaisi MH, Hamed I & Abdel Wahab AHA (2015) Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment. BioMed Research International, 2015, 1-12.
Ismail HMS, Hurd PJ, Khalil MIM, Kouzarides T, Bannister A & Gout I (2014) S6 Kinase 2 Is Bound to Chromatin-Nuclear Matrix Cellular Fractions and Is Able to Phosphorylate Histone H3 at Threonine 45 In Vitro and In Vivo. Journal of Cellular Biochemistry, 115(6), 1048-1062.
Ismail HMS, Myronova O, Tsuchiya Y, Niewiarowski A, Tsaneva I & Gout I (2013) Identification of the general transcription factor Yin Yang 1 as a novel and specific binding partner for S6 Kinase 2. Cellular Signalling, 25(5), 1054-1063.
Watt FE, Ismail HM, Didangelos A, Peirce M, Vincent TL, Wait R & Saklatvala J (2013) Src and fibroblast growth factor 2 independently regulate signaling and gene expression induced by experimental injury to intact articular cartilage. Arthritis & Rheumatism, 65(2), 397-407.
Ismail HMS (2012) Overexpression of S6 Kinase 1 in Brain Tumours Is Associated with Induction of Hypoxia-Responsive Genes and Predicts Patients' Survival. Journal of Oncology, 2012, 1-10.
Ismail HMS, Medhat AM, Karim AM & Zakhary NI (2011) Multiple Patterns ofFHITGene Homozygous Deletion in Egyptian Breast Cancer Patients. International Journal of Breast Cancer, 2011, 1-9.
Ismail HMS, Medhat AM, Karim AM & Zakhary NI (2011) FHIT gene and flanking region on chromosome 3p are subjected to extensive allelic loss in Egyptian breast cancer patients. Molecular Carcinogenesis, 50(8), 625-634.
Hurd PJ, Bannister AJ, Halls K, Dawson MA, Vermeulen M, Olsen JV, Ismail H, Somers J, Mann M, Owen-Hughes T , Gout I et al (2009) Phosphorylation of Histone H3 Thr-45 Is Linked to Apoptosis. Journal of Biological Chemistry, 284(24), 16575-16583.

Chapters

Ismail HM & Vincent TL (2017) Cartilage Injury and Osteoarthritis, Cartilage (pp. 27-40). Springer International Publishing

Conference proceedings papers

Zhu L, Chanalaris A, Ismail H, Wiberg A, Ng M, Watt FE, Furniss D, Gardiner M & Vincent TL (2019) Targeting retinoic acid metabolism as an anti-inflammatory treatment for hand osteoarthritis. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol. 100(4) (pp A31-A32)
Zhu L, Ismail H, Chanalaris A, Gardiner M & Vincent TL (2018) OP0261 Retinoic acid is regulated by cartilage injury and is anti-inflammatory in hand osteoarthritis. FRIDAY, 15 JUNE 2018
Ismail HM, Troeberg L, Vincent TL & Saklatvala J (2018) JNK-dependent modulation of the protease secretome profile of osteoarthritic cartilage. Osteoarthritis and Cartilage, Vol. 26 (pp S108-S109)
Zhu L, Ismail H, Chanalaris A, Muhammad H, Lympany S & Vincent TL (2018) Cartilage injury suppresses endogenous retinoic acid through activation of TGFβ-activated kinase 1 (TAK1). Osteoarthritis and Cartilage, Vol. 26 (pp S107-S107)
Ismail HM, Yamamoto K, Nagase H, Vincent TL, Troeberg L & Saklatvala J (2017) The interplay between JNK pathway activation, proteoglycan turnover and endocytosis in chondrocytes. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol. 98(3) (pp A17-A18)
Ismail HM, Chanalaris A, Miotla-Zarebska J, Vincent TL & Saklatvala J (2016) Differential inflammatory gene expression patterns in JNK2 knockout mice in response to IL1, cartilage injury and surgically induced osteoarthritis. Osteoarthritis and Cartilage, Vol. 24 (pp S146-S146)
Ismail HM, Yamamoto K, Vincent T, Nagase H, Troeberg L & Saklatvala J (2015) A significant role for the JNK pathway in regulating interleukin 1 induced-aggrecan degradation in human articular chondrocytes. Osteoarthritis and Cartilage, Vol. 23 (pp A152-A152)
Ismail HM, Zarebska J, Vincent T & Saklatvala J (2015) JNK2 knockout mice are significantly protected from surgically induced osteoarthritis. Osteoarthritis and Cartilage, Vol. 23 (pp A63-A64)
Ismail HM, Vincent TL & Saklatvala J (2014) The c-jun N-terminal kinase (JNK)-2 controls articular cartilage aggrecan degradation and progression of experimental osteoarthritis. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol. 95(3) (pp A16-A17)
Ismail HM, Vincent TL & Saklatvala J (2014) Wounding articular cartilage rapidly activates multiple signalling events in chondrocytes involving protein phosphorylation and polyubiquitination. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol. 95(3) (pp A16-A16)
Ismail HM, Sawaji Y & Saklatvala; J (2013) Interleukin 1 induces aggrecan degradation by human articular chondrocytes through a TAK1/MKK4/JNK2 pathway without involvement of NFKB. Osteoarthritis and Cartilage, Vol. 21 (pp S127-S127)

Preprints

Khalil MI, Ismail HM, Panasyuk G, Gout I & Pardo OE (2022) Asymmetric dimethylation of Ribosomal S6 Kinase 2 regulates its cellular localisation and pro-survival function, Cold Spring Harbor Laboratory.
Kaokhum N, Pinto-Fernández A, Wilkinson M, Kessler B & Ismail H () Ubiquitinome analysis of articular cartilage post mechanical injury reveals a differential ubiquitination pattern of a subset of DUBs and proteins linked to the ERAD cellular response, Cold Spring Harbor Laboratory.
Zhu L, Kamalathevan P, Koneva L, Zarebska JM, Chanalaris A, Ismail H, Wiberg A, Ng M, Muhammed H, Watt FE , Sansom S et al () Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis, Cold Spring Harbor Laboratory.

Teaching interests

I’m a fellow of the Higher Education Academy and currently a deputy lead on MolMed MED607 module (Mining Bioinformatics Data) and a lecturer on the following modules:

CDL610 Research Skills
CL416 Protein Network in Disease Models
CDL301 Cardiovascular Medicine: From Molecules to Man (Haemostasis and Thrombosis)
BIS330: Modelling Diseases

Professional activities and memberships

Versus Arthritis Bridging Research Fellow
Group leader at the Bateson Centre for disease models
Deputy lead of postgraduate research recruitment
PhD supervisor and personal academic tutor
Full member of British Biochemical society and International Society for Regenerative Biology