Dr. Dhiraj Kabra

EDUCATION

Doctor of Philosophy – Pharmacology and Toxicology, (Aug 2004-Oct 2009)
National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab, India,
Mentor Prof. Kulbhushan Tikoo

Master of Science – Pharmacology, and Toxicology, (July 2001-Dec 2002)
National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab, India
Mentor Prof. S.S Sharma

Bachler of Pharmacy: (July 1998-June 2001)
J. Chaturvedi College of Pharmacy, Nagpur university, Maharashtra, India

Diploma in Pharmacy (July 1996- June 1998)
Vidybharti College of Pharmacy, Amravati, Maharashtra, India
(Mumbai Technical Board)

RESEARCH, TEACHING, or OTHER INTERESTS

Endocrinology, Diabetes and Metabolism, Cancer Research, Cellular and Molecular Neuroscience, Molecular Biology

Scopus Publications

HDAC5 controls a hypothalamic STAT5b-TH axis, the sympathetic activation of ATP-consuming futile cycles and adult-onset obesity in male mice
Raian E. Contreras, Tim Gruber, Ismael González-García, Sonja C. Schriever, Meri De Angelis, et al.
Molecular Metabolism, 2024
Long-term adjustment of hepatic lipid metabolism after chronic stress and the role of FGF21
Matthias Dille, Aleksandra Nikolic, Natalie Wahlers, Pia Fahlbusch, Sylvia Jacob, et al.
Biochimica Et Biophysica Acta Molecular Basis of Disease, 2022
Histone deacetylase 5 regulates interleukin 6 secretion and insulin action in skeletal muscle
Oleksiy Klymenko, Tim Brecklinghaus, Matthias Dille, Christian Springer, Christian de Wendt, et al.
Molecular Metabolism, 2020
Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity
Sonja C. Schriever, Dhiraj G. Kabra, Katrin Pfuhlmann, Peter Baumann, Emily V. Baumgart, et al.
Journal of Clinical Investigation, 2020
Recent genome-wide association studies (GWAS) identified DUSP8, a dual-specificity phosphatase targeting MAP kinases, as type 2 diabetes (T2D) risk gene. Here, we unravel Dusp8 as gatekeeper in the hypothalamic control of glucose homeostasis in mice and humans. Male but not female Dusp8 loss-of-function mice, either with global or CRH neuron-specific deletion, had impaired systemic glucose tolerance and insulin sensitivity when exposed to high-fat diet (HFD). Mechanistically, we found impaired hypothalamic-pituitary-adrenal (HPA) axis feedback, blunted sympathetic responsiveness, and chronically elevated corticosterone levels driven by hypothalamic hyperactivation of Jnk signaling. Accordingly, global Jnk1 ablation, AAV-mediated Dusp8 overexpression in the mediobasal hypothalamus, or metyrapone-induced chemical adrenalectomy rescued the impaired glucose homeostasis of obese male Dusp8 KO mice, respectively. The sex-specific role of murine Dusp8 in governing hypothalamic Jnk signaling, insulin sensitivity and systemic glucose tolerance was consistent with fMRI data in human volunteers that revealed an association of the DUSP8 rs2334499 risk variant with hypothalamic insulin resistance in men. Further, expression of DUSP8 was increased in the infundibular nucleus of T2D humans. In summary, our findings suggest the GWAS-identified gene Dusp8 as novel hypothalamic factor that plays a functional role in the etiology of T2D.
Natural SIRT1 modifiers as promising therapeutic agents for improving diabetic wound healing
Pranav Kumar Prabhakar, Karmveer Singh, Dhiraj Kabra, Jeena Gupta
Phytomedicine, 2020
Phytochemicals enriched in spices: a source of natural epigenetic therapy
Jeena Gupta, Sandeep Sharma, Neeta Raj Sharma, Dhiraj Kabra
Archives of Pharmacal Research, 2020
Erratum. Celastrol-Induced Weight Loss Is Driven by Hypophagia and Independent From UCP1. Diabetes 2018;67:2456-2465
Katrin Pfuhlmann, Sonja C. Schriever, Peter Baumann, Dhiraj G. Kabra, Luke Harrison, et al.
Diabetes, 2019
In the article listed above, ERX was erroneously omitted from the duality of interest for Matthias H. …
Functional identity of hypothalamic melanocortin neurons depends on Tbx3
Carmelo Quarta, Alexandre Fisette, Yanjun Xu, Gustav Colldén, Beata Legutko, et al.
Nature Metabolism, 2019
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Peter Brown, Aik-Choon Tan, Mohamed A El-Esawi, Thomas Liehr, Oliver Blanck, et al.
Database, 2019
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
Celastrol-induced weight loss is driven by hypophagia and independent from UCP1
Katrin Pfuhlmann, Sonja C. Schriever, Peter Baumann, Dhiraj G. Kabra, Luke Harrison, et al.
Diabetes, 2018
Celastrol, a plant-derived constituent of traditional Chinese medicine, has been proposed to offer significant potential as an antiobesity drug. However, the molecular mechanism for this activity is unknown. We show that the weight-lowering effects of celastrol are driven by decreased food consumption. Although young Lepob mice respond with a decrease in food intake and body weight, adult Lepdb and Lepob mice are unresponsive to celastrol, suggesting that functional leptin signaling in adult mice is required to elicit celastrol’s catabolic actions. Protein tyrosine phosphatase 1 (PTP1B), a leptin negative-feedback regulator, has been previously reported to be one of celastrol’s targets. However, we found that global PTP1B knockout (KO) and wild-type (WT) mice have comparable weight loss and hypophagia when treated with celastrol. Increased levels of uncoupling protein 1 (UCP1) in subcutaneous white and brown adipose tissue suggest celastrol-induced thermogenesis as a further mechanism. However, diet-induced obese UCP1 WT and KO mice have comparable weight loss upon celastrol treatment, and celastrol treatment has no effect on energy expenditure under ambient housing or thermoneutral conditions. Overall, our results suggest that celastrol-induced weight loss is hypophagia driven and age-dependently mediated by functional leptin signaling. Our data encourage reconsideration of therapeutic antiobesity strategies built on leptin sensitization.
FGF21 regulates insulin sensitivity following long-term chronic stress
Tomas Jelenik, Matthias Dille, Sabrina Müller-Lühlhoff, Dhiraj G. Kabra, Zhou Zhou, et al.
Molecular Metabolism, 2018
Calcineurin A beta deficiency ameliorates HFD-induced hypothalamic astrocytosis in mice
Katrin Pfuhlmann, Sonja C. Schriever, Beata Legutko, Peter Baumann, Luke Harrison, et al.
Journal of Neuroinflammation, 2018
Absence of the kinase S6k1 mimics the effect of chronic endurance exercise on glucose tolerance and muscle oxidative stress
C. Binsch, T. Jelenik, A. Pfitzer, M. Dille, S. Müller-Lühlhoff, et al.
Molecular Metabolism, 2017
Alterations in neuronal control of body weight and anxiety behavior by glutathione peroxidase 4 deficiency
Sonja C. Schriever, Annemarie Zimprich, Katrin Pfuhlmann, Peter Baumann, Florian Giesert, et al.
Neuroscience, 2017
Hypothalamic leptin action is mediated by histone deacetylase 5
Dhiraj G. Kabra, Katrin Pfuhlmann, Cristina García-Cáceres, Sonja C. Schriever, Veronica Casquero García, et al.
Nature Communications, 2016
Calcineurin Links Mitochondrial Elongation with Energy Metabolism
Paul T. Pfluger, Dhiraj G. Kabra, Michaela Aichler, Sonja C. Schriever, Katrin Pfuhlmann, et al.
Cell Metabolism, 2015
Tachykinin-1 in the central nervous system regulates adiposity in rodents
Chitrang Trivedi, Xiaoye Shan, Yi-Chun Loraine Tung, Dhiraj Kabra, Jenna Holland, et al.
Endocrinology United States, 2015
Ablation of Ghrelin O-Acyltransferase Does Not Improve Glucose Intolerance or Body Adiposity in Mice on a Leptin-Deficient ob/ob Background
Henriette Kirchner, Kristy M. Heppner, Jenna Holland, Dhiraj Kabra, Matthias H. Tschöp, et al.
Plos One, 2013
P62 Links β-adrenergic input to mitochondrial function and thermogenesis
Timo D. Müller, Sang Jun Lee, Martin Jastroch, Dhiraj Kabra, Kerstin Stemmer, et al.
Journal of Clinical Investigation, 2013
High calorie diet triggers hypothalamic angiopathy
Chun-Xia Yi, Martin Gericke, Martin Krüger, Anneke Alkemade, Dhiraj G. Kabra, et al.
Molecular Metabolism, 2012
Targeted estrogen delivery reverses the metabolic syndrome
Brian Finan, Bin Yang, Nickki Ottaway, Kerstin Stemmer, Timo D Müller, et al.
Nature Medicine, 2012
The goat-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction
Chun-Xia Yi, Kristy M. Heppner, Henriette Kirchner, Jenny Tong, Maximillian Bielohuby, et al.
Plos One, 2012
Contribution of formulation and excipients towards enhanced permeation of curcumin
B. Wahlang, D. Kabra, Y. Pawar, K. Tikoo, A. Bansal
Arzneimittel Forschung Drug Research, 2012
Pharmacological treatment of obesity
Dhiraj G. Kabra, Uma D. Kabra, Matthias H. Tschöp, Susanna Hofmann
Sleep Loss and Obesity Intersecting Epidemics, 2012
Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21
Timo D. Müller, Lorraine M. Sullivan, Kirk Habegger, Chun‐Xia Yi, Dhiraj Kabra, et al.
Journal of Peptide Science, 2012
Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts
Dhiraj G. Kabra, Jeena Gupta, Kulbhushan Tikoo
Biochimica Et Biophysica Acta Molecular Basis of Disease, 2009
Change in histone H3 phosphorylation, MAP kinase p38, SIR 2 and p53 expression by resveratrol in preventing streptozotocin induced type I diabetic nephropathy
Kulbhushan Tikoo, Karmveer Singh, Dhiraj Kabra, Vikram Sharma, Anil Gaikwad
Free Radical Research, 2008
Change in post-translational modifications of histone H3, heat-shock protein-27 and MAP kinase p38 expression by curcumin in streptozotocin-induced type I diabetic nephropathy
K Tikoo, R L Meena, D G Kabra, A B Gaikwad
British Journal of Pharmacology, 2008
Differential effects of tannic acid on cisplatin induced nephrotoxicity in rats
Kulbhushan Tikoo, Deepak Kumar Bhatt, Anil Bhanudas Gaikwad, Vikram Sharma, Dhiraj G. Kabra
FEBS Letters, 2007
Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53
Kulbhushan Tikoo, Durga Nand Tripathi, Dhiraj G. Kabra, Vikram Sharma, Anil Bhanudas Gaikwad
FEBS Letters, 2007
Neuroprotective effect of 4-amino-1,8-napthalimide, a poly(ADP ribose) polymerase inhibitor in middle cerebral artery occlusion-induced focal cerebral ischemia in rat
Dhiraj G Kabra, Meenakshisundaram Thiyagarajan, Chaman L Kaul, Shyam S Sharma
Brain Research Bulletin, 2004

RECENT SCHOLAR PUBLICATIONS

Medicinal chemistry advances of SGLT inhibitors: SAR, structural innovation, and mechanistic insights
UD Kabra, MJ Umekar, DG Kabra
European Journal of Medicinal Chemistry 308, 118707 , 2026
2026
HDAC5 controls a hypothalamic STAT5b-TH axis, the sympathetic activation of ATP-consuming futile cycles and adult-onset obesity in male mice
RE Contreras, T Gruber, I González-García, SC Schriever, M De Angelis, ...
Molecular Metabolism 90, 102033 , 2024
2024
Citations: 2
Long-term adjustment of hepatic lipid metabolism after chronic stress and the role of FGF21
M Dille, A Nikolic, N Wahlers, P Fahlbusch, S Jacob, S Hartwig, S Lehr, ...
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1868 (1), 166286 , 2022
2022
Citations: 16
Histone deacetylase 5 regulates interleukin 6 secretion and insulin action in skeletal muscle
O Klymenko, T Brecklinghaus, M Dille, C Springer, C de Wendt, ...
Molecular Metabolism 42, 101062 , 2020
2020
Citations: 39
Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity
SC Schriever, DG Kabra, K Pfuhlmann, P Baumann, EV Baumgart, ...
The Journal of clinical investigation 130 (11), 6093-6108 , 2020
2020
Citations: 42
Natural SIRT1 modifiers as promising therapeutic agents for improving diabetic wound healing
PK Prabhakar, K Singh, D Kabra, J Gupta
Phytomedicine 76, 153252 , 2020
2020
Citations: 49
Phytochemicals enriched in spices: a source of natural epigenetic therapy
J Gupta, S Sharma, NR Sharma, D Kabra
Archives of pharmacal research 43 (2), 171-186 , 2020
2020
Citations: 21
Functional identity of hypothalamic melanocortin neurons depends on Tbx3
C Quarta, A Fisette, Y Xu, G Colldén, B Legutko, YT Tseng, A Reim, ...
Nature metabolism 1 (2), 222-235 , 2019
2019
Citations: 55
Celastrol-induced weight loss is driven by hypophagia and independent from UCP1
K Pfuhlmann, SC Schriever, P Baumann, DG Kabra, L Harrison, ...
Diabetes 67 (11), 2456-2465 , 2018
2018
Citations: 49
FGF21 regulates insulin sensitivity following long-term chronic stress
T Jelenik, M Dille, S Müller-Lühlhoff, DG Kabra, Z Zhou, C Binsch, ...
Molecular metabolism 16, 126-138 , 2018
2018
Citations: 29
Calcineurin A beta deficiency ameliorates HFD-induced hypothalamic astrocytosis in mice
K Pfuhlmann, SC Schriever, B Legutko, P Baumann, L Harrison, ...
Journal of Neuroinflammation 15 (1), 35 , 2018
2018
Citations: 9
Absence of the kinase S6k1 mimics the effect of chronic endurance exercise on glucose tolerance and muscle oxidative stress
C Binsch, T Jelenik, A Pfitzer, M Dille, S Müller-Lühlhoff, S Hartwig, ...
Molecular metabolism 6 (11), 1443-1453 , 2017
2017
Citations: 19
Alterations in neuronal control of body weight and anxiety behavior by glutathione peroxidase 4 deficiency
SC Schriever, A Zimprich, K Pfuhlmann, P Baumann, F Giesert, V Klaus, ...
Neuroscience 357, 241-254 , 2017
2017
Citations: 62
Hypothalamic leptin action is mediated by histone deacetylase 5
DG Kabra, K Pfuhlmann, C García-Cáceres, SC Schriever, ...
Nature Communications 7 (1), 10782 , 2016
2016
Citations: 92
Calcineurin links mitochondrial elongation with energy metabolism
PT Pfluger, DG Kabra, M Aichler, SC Schriever, K Pfuhlmann, VC García, ...
Cell metabolism 22 (5), 838-850 , 2015
2015
Citations: 111
Tachykinin-1 in the central nervous system regulates adiposity in rodents
C Trivedi, X Shan, YCL Tung, D Kabra, J Holland, S Amburgy, K Heppner, ...
Endocrinology 156 (5), 1714-1723 , 2015
2015
Citations: 19
Ablation of ghrelin O-acyltransferase does not improve glucose intolerance or body adiposity in mice on a leptin-deficient ob/ob background
H Kirchner, KM Heppner, J Holland, D Kabra, MH Tschöp, PT Pfluger
PLoS One 8 (4), e61822 , 2013
2013
Citations: 31
p62 links β-adrenergic input to mitochondrial function and thermogenesis
TD Müller, SJ Lee, M Jastroch, D Kabra, K Stemmer, M Aichler, ...
The Journal of clinical investigation 123 (1) , 2012
2012
Citations: 163
High calorie diet triggers hypothalamic angiopathy
CX Yi, M Gericke, M Krüger, A Alkemade, DG Kabra, S Hanske, J Filosa, ...
Molecular metabolism 1 (1-2), 95-100 , 2012
2012
Citations: 80
Targeted estrogen delivery reverses the metabolic syndrome
B Finan, B Yang, N Ottaway, K Stemmer, TD Müller, CX Yi, K Habegger, ...
Nature Medicine 18 (12), 1847–1856 , 2012
2012
Citations: 350

MOST CITED SCHOLAR PUBLICATIONS

Targeted estrogen delivery reverses the metabolic syndrome
B Finan, B Yang, N Ottaway, K Stemmer, TD Müller, CX Yi, K Habegger, ...
Nature Medicine 18 (12), 1847–1856 , 2012
2012
Citations: 350
Restoration of leptin responsiveness in diet‐induced obese mice using an optimized leptin analog in combination with exendin‐4 or FGF21
TD Müller, LM Sullivan, K Habegger, CX Yi, D Kabra, E Grant, N Ottaway, ...
Journal of Peptide Science 18 (6), 383-93 , 2012
2012
Citations: 193
Intermittent fasting prevents the progression of type I diabetic nephropathy in rats and changes the expression of Sir2 and p53
K Tikoo, DN Tripathi, DG Kabra, V Sharma, AB Gaikwad
FEBS letters 581 (5), 1071-1078 , 2007
2007
Citations: 175
Change in post‐translational modifications of histone H3, heat‐shock protein‐27 and MAP kinase p38 expression by curcumin in streptozotocin‐induced type I diabetic nephropathy
K Tikoo, RL Meena, DG Kabra, AB Gaikwad
British journal of pharmacology 153 (6), 1225-1231 , 2008
2008
Citations: 173
p62 links β-adrenergic input to mitochondrial function and thermogenesis
TD Müller, SJ Lee, M Jastroch, D Kabra, K Stemmer, M Aichler, ...
The Journal of clinical investigation 123 (1) , 2012
2012
Citations: 163
Calcineurin links mitochondrial elongation with energy metabolism
PT Pfluger, DG Kabra, M Aichler, SC Schriever, K Pfuhlmann, VC García, ...
Cell metabolism 22 (5), 838-850 , 2015
2015
Citations: 111
Differential effects of tannic acid on cisplatin induced nephrotoxicity in rats
K Tikoo, DK Bhatt, AB Gaikwad, V Sharma, DG Kabra
FEBS letters 581 (10), 2027-2035 , 2007
2007
Citations: 100
Change in histone H3 phosphorylation, MAP kinase p38, SIR 2 and p53 expression by resveratrol in preventing streptozotocin induced type I diabetic nephropathy
K Tikoo, K Singh, D Kabra, V Sharma, A Gaikwad
Free radical research 42 (4), 397-404 , 2008
2008
Citations: 97
Hypothalamic leptin action is mediated by histone deacetylase 5
DG Kabra, K Pfuhlmann, C García-Cáceres, SC Schriever, ...
Nature Communications 7 (1), 10782 , 2016
2016
Citations: 92
High calorie diet triggers hypothalamic angiopathy
CX Yi, M Gericke, M Krüger, A Alkemade, DG Kabra, S Hanske, J Filosa, ...
Molecular metabolism 1 (1-2), 95-100 , 2012
2012
Citations: 80
The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction
CX Yi, KM Heppner, H Kirchner, J Tong, M Bielohuby, BD Gaylinn, ...
PLoS One 7 (2), e32100 , 2012
2012
Citations: 63
Alterations in neuronal control of body weight and anxiety behavior by glutathione peroxidase 4 deficiency
SC Schriever, A Zimprich, K Pfuhlmann, P Baumann, F Giesert, V Klaus, ...
Neuroscience 357, 241-254 , 2017
2017
Citations: 62
Neuroprotective effect of 4-amino-1, 8-napthalimide, a poly (ADP ribose) polymerase inhibitor in middle cerebral artery occlusion-induced focal cerebral ischemia in rat
DG Kabra, M Thiyagarajan, CL Kaul, SS Sharma
Brain Research Bulletin 62 (5), 425-433 , 2004
2004
Citations: 56
Functional identity of hypothalamic melanocortin neurons depends on Tbx3
C Quarta, A Fisette, Y Xu, G Colldén, B Legutko, YT Tseng, A Reim, ...
Nature metabolism 1 (2), 222-235 , 2019
2019
Citations: 55
Natural SIRT1 modifiers as promising therapeutic agents for improving diabetic wound healing
PK Prabhakar, K Singh, D Kabra, J Gupta
Phytomedicine 76, 153252 , 2020
2020
Citations: 49
Celastrol-induced weight loss is driven by hypophagia and independent from UCP1
K Pfuhlmann, SC Schriever, P Baumann, DG Kabra, L Harrison, ...
Diabetes 67 (11), 2456-2465 , 2018
2018
Citations: 49
Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity
SC Schriever, DG Kabra, K Pfuhlmann, P Baumann, EV Baumgart, ...
The Journal of clinical investigation 130 (11), 6093-6108 , 2020
2020
Citations: 42
Histone deacetylase 5 regulates interleukin 6 secretion and insulin action in skeletal muscle
O Klymenko, T Brecklinghaus, M Dille, C Springer, C de Wendt, ...
Molecular Metabolism 42, 101062 , 2020
2020
Citations: 39
Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts
DG Kabra, J Gupta, K Tikoo
Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1792 (6), 574-583 , 2009
2009
Citations: 38
Ablation of ghrelin O-acyltransferase does not improve glucose intolerance or body adiposity in mice on a leptin-deficient ob/ob background
H Kirchner, KM Heppner, J Holland, D Kabra, MH Tschöp, PT Pfluger
PLoS One 8 (4), e61822 , 2013
2013
Citations: 31

GRANT DETAILS

HDAC5 links epigenetic chromatin remodeling with the pathogenesis of obesity and glucose intolerance.
DZD Germany
50,000 Euro

INDUSTRY EXPERIENCE

In my last position at SPARC (2008-2004), I have led more than 12 scientists and developed a range of molecular biology techniques within the field of preclinical pharmacology to characterize pharmacodynamic biomarkers using immunohistochemistry (IHC), quantitative PCR (qPCR), and western blotting. Additionally, I have written, reviewed, and edited Investigational New Drug (IND) reports and Investigator's Brochures (IB) documents. At SPARC, I have actively participated in due diligence exercises to evaluate external projects and contribute to internal ideation programs. I have also served as the operational head of the department for 2 years. Under my leadership, my team has been recognized with 4 Shining Star awards for their outstanding performance.