Grzegorz Walkiewicz

All Publications

• TIGRa: An ultra-compact programmable activator enabling multiplexed and efficient gene regulation. Cell stem cell Liu, Z., Chen, S., Wang, W., Zhang, F., Wang, Q., Walkiewicz, G., Hossen, F., Zhou, J., Wang, Y., Sun, Y. 2026

  Abstract

  Programmable gene activation has broad therapeutic potential but remains constrained by the large effector size, limited multiplexing capacity, and challenges in in vivo delivery. Here, we develop the TIGR-TasR-mediated activator (TIGRa), a compact transcriptional activator derived from the tandem interspaced guide RNA (TIGR)-TIGR-associated protein (TasR) system that is mechanistically distinct from CRISPR-based activators. TIGRa is less than half the size of dSpCas9-based activators while achieving comparable or greater activation efficiency. Its native TIGR array architecture enables efficient multiplexed regulation, supporting simultaneous activation of up to 12 endogenous genes from a single compact construct. TIGRa-mediated multi-gene activation efficiently reprogrammed human fibroblasts into induced pluripotent stem cells. In addition, an all-in-one adeno-associated virus (AAV)-TIGRa vector activated endogenous CaMKII in vivo, promoting retinal ganglion cell survival and preserving visual function in a mouse model of N-methyl-D-aspartic (NMDA)-induced retinal injury. These results establish TIGRa as a compact and multiplexable platform for therapeutic gene regulation and in vivo genetic medicine.

  View details for DOI 10.1016/j.stem.2026.07.008

  View details for PubMedID 42575098

• Circulating Brain-Related miRNAs as Predictors of Postoperative Delirium in Cardiac Surgery Patients. International journal of molecular sciences Nowakowska, K., Walkiewicz, G., Stec-Martyna, E., Kulczycka-Wojdala, D., Frankowska, E., Miler, P., Pawlak, A., Woźniak, K., Krejca, M., Wilczyński, M., Kazmierski, J. 2025; 26 (18)

  Abstract

  Delirium is a neuropsychiatric syndrome that is pathophysiologically related to both mental (dementia, depression) and physical illness. Its occurrence results in a poor prognosis. This study investigates whether specific miRNAs (miR-9-3p, miR-34c-5p, miR-96-5p, miR-183-5p, and miR-374-3p) related to brain function are associated with an increased risk of postoperative delirium. A total of 224 adult individuals scheduled for elective cardiac surgery were eligible to participate in the study. Delirium diagnosis was established with the use of the Confusion Assessment Method. Following miRNA expression profiling, cDNA synthesis was conducted on the samples obtained one day before and the day after surgery, from 60 delirium patients and 60 randomly selected non-delirium individuals. Univariate comparisons revealed that preoperative miR-96-5p (p = 0.05) and miR-183-5p (p = 0.001), along with postoperative miR-34c-5p (p = 0.009), miR-96-5p (p = 0.07), and miR-183-5p (p = 0.05), were associated with the risk of post-surgery delirium. However, after conducting multivariate logistic regression analysis, only miR-183-5p was found to be independently associated with the risk of delirium development. Other predictors of delirium included an ongoing episode of depression, peripheral vascular disease, female gender, active smoking, and increased postoperative pCO2 concentration. The current study revealed that preoperatively decreased expression of miR-183-5p predicts delirium development after cardiac surgery.

  View details for DOI 10.3390/ijms26189062

  View details for PubMedID 41009624

  View details for PubMedCentralID PMC12470073

• pTau pathology in the retina of TAU58 mice: association with ganglion cell degeneration and implications on seeding and propagation of pTau from human brain lysates ACTA NEUROPATHOLOGICA COMMUNICATIONS Walkiewicz, G., Ronisz, A., Ospitalieri, S., Tsaka, G., Tome, S. O., Vandenberghe, R., von Arnim, C. A. F., Rousseau, F., Schymkowitz, J., De Groef, L., Thal, D. 2024; 12 (1): 194

  Abstract

  The accumulation of abnormal phosphorylated Tau protein (pTau) in neurons of the brain is a pathological hallmark of Alzheimer's disease (AD). PTau pathology also occurs in the retina of AD cases. Accordingly, questions arise whether retinal pTau can act as a potential seed for inducing cerebral pTau pathology and whether retinal pTau pathology causes degeneration of retinal neurons. To address these questions, we (1) characterized pTau pathology in the retina of TAU58 mice, (2) determined the impact of pTau pathology on retinal ganglion cell density, and (3) used this mouse model to test whether brain lysates from AD and/or non-AD control cases induce seeding in the retina and/or propagation into the brain. TAU58 mice developed retinal pTau pathology at 6 months of age, increasing in severity and extent with age. TAU58 mice showed reduced retinal ganglion cell density compared to wild-type mice, which declined with age and pTau pathology progression. Brain lysates from non-AD Braak neurofibrillary tangle (NFT) stage I controls increased retinal pTau pathology after subretinal injection compared to phosphate-buffered saline (PBS) but did not accelerate pTau pathology in the brain. In contrast, subretinally injected AD brain lysates accelerated pTau pathology in the retina and the contralateral superior colliculus. Subretinal injection of AD brain lysates, but not of non-AD brain, induced in this context a neuroinflammatory response in the retina and in the contralateral primary visual cortex. These results lead to the following conclusions: (1) Brain lysates from AD and non-AD sources can accelerate tauopathy within the retina. (2) The anterograde propagation of pTau pathology from the retina to the brain can be triggered by subretinal injections of AD brain lysates. (3) Such subretinal injections also provoke a neuroinflammatory response in both the retina and the visual cortex. (4) The accumulation of retinal pTau is associated with the degeneration of the involved ganglion cells, indicating that retinal tauopathy might contribute to vision impairment in the elderly and underscore the retina's potential role in spreading tau pathology to the brain.

  View details for DOI 10.1186/s40478-024-01907-8

  View details for Web of Science ID 001380874000006

  View details for PubMedID 39707519

  View details for PubMedCentralID PMC11662635

• Primary retinal tauopathy: A tauopathy with a distinct molecular pattern ALZHEIMERS & DEMENTIA Walkiewicz, G., Ronisz, A., Van Ginderdeuren, R., Lemmens, S., Bouwman, F. H., Hoozemans, J. J. M., Morrema, T. H. J., Rozemuller, A. J., Hart de Ruyter, F. J., De Groef, L., Stalmans, I., Thal, D. 2024; 20 (1): 330-340

  Abstract

  Phosphorylated tau (p-tau) accumulation, a hallmark of Alzheimer's disease (AD), can also be found in the retina. However, it is uncertain whether it is linked to AD or another tauopathy.Retinas from 164 individuals, with and without AD, were analyzed for p-tau accumulation and its relationship with age, dementia, and vision impairment.Retinal p-tau pathology showed a consistent pattern with four stages and a molecular composition distinct from that of cerebral tauopathies. The stage of retinal p-tau pathology correlated with age (r = 0.176, P = 0.024) and was associated with AD (odds ratio [OR] 3.193; P = 0.001), and inflammation (OR = 2.605; P = 0.001). Vision impairment was associated with underlying eye diseases (β = 0.292; P = 0.001) and the stage of retinal p-tau pathology (β = 0.192; P = 0.030) in a linear regression model.The results show the presence of a primary retinal tauopathy that is distinct from cerebral tauopathies.

  View details for DOI 10.1002/alz.13424

  View details for Web of Science ID 001080274400001

  View details for PubMedID 37615275

  View details for PubMedCentralID PMC10916964

• Increased postoperative myeloperoxidase concentration associated with low baseline antioxidant capacity as the risk factor of delirium after cardiac surgery ANNALS OF MEDICINE Kazmierski, J., Miler, P., Pawlak, A., Jerczynska, H., Nowakowska, K., Walkiewicz, G., Wozniak, K., Krejca, M., Wilczynski, M. 2022; 54 (1): 610-616

  Abstract

  Though risk factors of postoperative delirium are well described, its pathophysiology is still undiscovered. The primary objective of the current study is to assess whether increased pre- and postoperative myeloperoxidase (MPO) levels are associated with postoperative delirium in the population of cardiac surgery patients. The secondary objective is to evaluate the correlation between MPO levels and serum antioxidant capacity (AC).The patients' cognitive status was assessed one day preoperatively with the use of the Mini-Mental State Examination Test and the Clock Drawing Test. A diagnosis of major depressive disorder and anxiety disorders was established based on DSM-5 criteria. Blood samples for MPO and AC levels were collected both pre- and postoperatively. The Confusion Assessment Method for the Intensive Care Unit was used to screen for a diagnosis of delirium.Delirium occurred in 34% (61 of 177) of patients. Multivariable logistic regression analysis revealed that increased postoperative MPO concentration was independently associated with postoperative delirium development, and negatively correlated with lower baseline serum AC.Cardiac surgery patients with less efficient antioxidative mechanisms experience a higher postoperative peak of serum MPO, which in turn may predispose to postoperative delirium development.KEY MESSAGESMPO is a lysosomal enzyme with strong pro-oxidative and pro-inflammatory properties.Cardiac surgery patients who have increased concentration of postoperative MPO are at significantly higher risk of postoperative delirium development.This higher level of postoperative MPO is negatively correlated with baseline antioxidant capacity (AC).It can be hypothesized that individuals with decreased baseline AC experience a higher peak of MPO post-surgery due to less efficient antioxidative mechanisms, which in turn contributes to postoperative delirium development.

  View details for DOI 10.1080/07853890.2022.2039405

  View details for Web of Science ID 000757017300001

  View details for PubMedID 35175161

  View details for PubMedCentralID PMC8856092

• The effect of drugs used in allergic rhinitis on the central nervous system ALERGOLOGIA POLSKA-POLISH JOURNAL OF ALLERGOLOGY Walkiewicz, G., Jankowska, M., Pawliczak, R. 2020; 7 (4): 190-196

  View details for DOI 10.5114/pja.2020.102085

  View details for Web of Science ID 000615580100003

• Allergic rhinitis and central nervous system disorders ALERGOLOGIA POLSKA-POLISH JOURNAL OF ALLERGOLOGY Walkiewicz, G., Sobolczyk, M., Pawliczak, R. 2020; 7 (2): 88-92

  View details for DOI 10.5114/pja.2020.96128

  View details for Web of Science ID 000543492300004